Decoding ACO1: Metabolic Regulation, Disease Association and Precision Detection System of a Bifunctional Core Protein
Within the sophisticated human life‑regulatory network lies a class of “multifunctional hub proteins”. A single molecule can switch functional modes and simultaneously govern cellular energy metabolism and metal‑ion homeostasis. ACO1 (Aconitase 1, also known as IRP1) serves as a prime representative of this protein family. As a bifunctional cytosolic protein with both enzymatic catalytic and gene‑regulatory activities, ACO1 is extensively involved in pivotal physiological processes including tricarboxylic acid (TCA) cycle‑driven energy metabolism, cellular iron homeostasis modulation, and oxidative‑stress response. Its functional dysregulation is tightly linked to the onset and progression of multiple severe disorders such as tumours, neurodegenerative diseases and haematological diseases. In‑depth dissection of the molecular properties, action mechanisms, disease relevance and detection technologies of ACO1 is of great significance for exploring biological mechanisms, discovering disease therapeutic targets, and advancing precision diagnosis and therapy.
I. Basic Information of ACO1: A Unique Bifunctional Hub Protein
ACO1 is a highly conserved functional gene encoded by the human genome, with Gene ID 48. Its aliases include IRP1, ACONS, IREBP1, etc. Localized in the cytoplasm, it represents the cytosolic isoform distinct from mitochondrial aconitase ACO2. It is widely expressed in various human tissues and cells, with markedly elevated expression in organs featuring vigorous metabolism and high iron demand.
In terms of molecular structure, ACO1 is a typical iron-sulfur protein whose core structure contains the critical [4Fe-4S] iron-sulfur cluster cofactor. This unique structure serves as the fundamental basis for its bifunctional switch. Unlike conventional monofunctional proteins, ACO1 does not undergo drastic fluctuations in expression level; instead, it switches functional modes merely via qualitative structural changes, acting as a core "switch" in physiological homeostasis regulation. The protein sequence of ACO1 is highly conserved throughout evolution, confirming its irreplaceable regulatory role in eukaryotic life activities.
Physiologically, ACO1 undertakes two core tasks: it functions as a metabolic enzyme participating in cellular energy cycling on one hand, and acts as a regulatory protein governing iron metabolic homeostasis on the other. These dual functions synergize and restrict each other to maintain normal cellular physiological status. Dysfunction directly leads to cellular metabolic disorders and pathological damage.
II. Mechanism of Action of ACO1: Precise Bifunctional Regulation Mediated by Iron-Sulfur Switch
The core regulatory logic of ACO1 lies in an iron-sulfur cluster-dependent functional switch mechanism. It can precisely sense intracellular iron concentration and oxidative stress status, dynamically toggling between the “metabolic enzyme form” and “gene regulatory protein form” without altering total protein abundance, thereby achieving fine-tuned regulation of cellular metabolism and iron homeostasis.
1. Iron-replete state: Exerts aconitase catalytic function
When intracellular iron levels are sufficient and the oxidative environment remains stable, ACO1 binds an intact [4Fe-4S] iron-sulfur cluster to form a fully active holoenzyme. In this state, it acts as a key enzyme in the tricarboxylic acid (TCA) cycle. It specifically catalyzes the isomerization of citrate into isocitrate to sustain continuous TCA cycle flux, supporting cellular glucose metabolism and energy production. Meanwhile, it promotes NADPH generation, preserves the reduced state of intracellular glutathione, mitigates oxidative stress damage, and maintains normal cellular proliferation and metabolic rhythm.
2. Iron-deficient / stress state: Switches to iron regulatory protein function
Under conditions of cellular iron deprivation, reactive oxygen species (ROS) accumulation or hypoxic stress, the [4Fe-4S] iron-sulfur cluster of ACO1 rapidly disassembles, triggering conformational changes in the protein. It loses enzymatic catalytic activity and converts into apoprotein (apoIRP1). The remodeled ACO1 acquires strong RNA-binding capacity and specifically binds to iron-responsive elements (IREs) on target mRNAs, modulating the expression of iron-metabolism-related genes via post-transcriptional regulation.
This regulation exhibits strict site specificity: binding to the 5′ untranslated region (5′UTR) of target mRNAs represses translation of ferritin, mitochondrial ACO2 and other proteins, reducing iron storage and mitochondrial metabolic consumption. Binding to the 3′ untranslated region (3′UTR) protects mRNAs of transferrin receptor 1 (TfR1) and divalent metal transporter 1 (DMT1) from degradation, facilitating iron uptake and transport. Through this mechanism, ACO1 rapidly boosts cellular iron acquisition, minimizes iron loss, restores cellular iron homeostasis, and adapts cellular metabolism under stress.
3. Coordinated regulation of downstream signaling pathways
Beyond core iron and energy metabolism control, ACO1 further modulates cellular physiology via extended axes including the ACO1–HIF-2α axis and ferroptosis pathway. By regulating the expression and activity of hypoxia-inducible factor HIF-2α, it participates in systemic oxygen sensing, erythropoiesis and vascular remodeling. As a critical upstream regulator of ferroptosis, it governs cellular iron overload and lipid peroxidation levels to determine the progression of programmed cell death, interconnecting a multi-layered regulatory network spanning metabolism, stress response and cell death.
III. Association of ACO1 with Diseases: A Key Regulatory Target for Multifarious Diseases
Dysfunction of ACO1 directly disrupts cellular iron homeostasis and energy metabolic balance, triggering a cascade of pathological alterations including oxidative stress, metabolic disorders and dysregulated apoptosis. It is extensively involved in the initiation and progression of multiple severe disorders such as tumors, neurodegenerative diseases, hematological diseases and fibrotic diseases, rendering it a highly promising diagnostic biomarker and therapeutic target.
1. Malignant tumors: Regulation of tumor proliferation and ferroptosis evasion
ACO1 exhibits specific downregulation in a variety of tumors. The decreased expression of ACO1 serves as a critical mechanism enabling tumor cells to evade ferroptosis and sustain unlimited proliferation. In malignancies including hepatocellular carcinoma, non‑small cell lung cancer and endometrial carcinoma, reduced ACO1 expression disturbs cellular iron metabolism and causes aberrant iron accumulation. Meanwhile, it suppresses iron‑dependent lipid peroxidation‑mediated programmed cell death, supporting tumor cell survival.
In addition, ACO1 modulates the tumor microenvironment via the HIF‑2α pathway. ACO1 depletion markedly increases HIF‑2α protein accumulation in tumor cells and activates oncogenic pathways such as c‑Myc and TGFα. This promotes tumor cell proliferation, invasion and metastasis, and mediates tumor angiogenesis to accelerate disease progression. Clinical studies have verified that ACO1 expression level is strongly correlated with tumor stage and prognosis; patients with low ACO1 expression carry a higher risk of recurrence and shorter survival time.
2. Neurodegenerative diseases: Mediation of brain iron accumulation and neuronal injury
Disrupted brain iron homeostasis represents a core pathological hallmark of neurodegenerative diseases, and ACO1 acts as the central protein governing brain iron metabolism. In disorders such as Parkinson’s disease and Huntington’s disease, ACO1 activity is abnormally elevated in patients’ brain tissues, which overactivates the expression of iron transporter DMT1 and leads to excessive iron deposition in critical brain regions including the substantia nigra and striatum.
Excessive iron buildup induces robust oxidative stress, reduces cerebral glutathione antioxidant capacity and triggers ferroptotic death of dopaminergic neurons. Meanwhile, aberrant ACO1 function suppresses the expression of mitochondrial ACO2 and impairs energy production in the tricarboxylic acid cycle, resulting in energy metabolism failure in neurons. Ultimately, this leads to degenerative neuronal damage and progressive clinical manifestations such as motor dysfunction and cognitive decline.
3. Hematological and cardiovascular diseases: Regulation of erythropoiesis and vascular homeostasis
The ACO1–HIF2α axis constitutes an essential regulatory pathway for hematological homeostasis. ACO1 gene defects or functional inactivation cause abnormal overexpression of renal HIF2α, which continuously stimulates massive secretion of erythropoietin (EPO) and leads to secondary polycythemia. Moreover, HIF2α activation in pulmonary endothelial cells upregulates endothelin 1 expression, inducing vasoconstriction, pulmonary hypertension and other cardiovascular lesions. Besides, in iron metabolic disorders during pregnancy, placental ACO1 dysfunction results in insufficient iron acquisition by the fetus and elevates the risk of iron‑deficiency anemia in newborns.
4. Fibrotic diseases: Involvement in tissue remodeling and disease progression
Studies on idiopathic pulmonary fibrosis confirm that aberrant ACO1 expression in pulmonary blood vessels is highly synchronized with fibrotic progression. Under pathological conditions with impaired mitochondrial metabolism, ACO1‑mediated cytoplasmic metabolic disturbance and iron homeostasis imbalance promote abnormal proliferation of pulmonary fibroblasts and excessive extracellular matrix deposition, accelerating the progression of pulmonary fibrosis. Thus, ACO1 acts as a valuable auxiliary biomarker for disease advancement of pulmonary fibrosis.
IV. ACO1 Detection Technology: A Precise System from Molecular Quantification to Activity Characterization
Accurate detection of ACO1 gene expression, protein abundance and enzymatic activity serves as core support for deciphering its physiological functions, linking pathological mechanisms of diseases and exploring its clinical translational value. At present, ACO1 detection has established a comprehensive technical system covering gene, protein and enzymatic activity levels, catering to diverse scenarios including basic research, clinical sample screening and target validation.
1. Gene-level detection: Nucleic acid quantification and mutation analysis
Quantitative real-time PCR (qRT-PCR) is the primary technique. Total RNA is extracted from cell or tissue samples, and target ACO1 fragments are amplified using specific primers to precisely quantify ACO1 mRNA expression levels. This method rapidly identifies aberrant fluctuations in ACO1 gene transcription in samples and is suitable for large-scale preliminary screening and differential analysis between disease and control groups. Combined with gene sequencing, it can detect ACO1 gene mutations and polymorphic loci, elucidate the mechanisms of functional defects caused by genetic variants, and provide evidence for tracing the etiology of hereditary iron metabolic disorders.
2. Protein-level detection: Qualitative localization and precise quantification
This represents the most commonly applied core dimension of ACO1 detection, with multiple well-established techniques available for different testing requirements:
- Western Blot (WB): Utilizes ACO1-specific antibodies for qualitative and semi-quantitative detection of ACO1 protein in samples. It reliably identifies differences in protein expression, featuring simple operation and high specificity, and is widely adopted to verify protein expression levels in basic research.
- Immunohistochemistry (IHC) / Immunofluorescence (ICC/IF): Enables tissue and cellular localization of ACO1 protein, clearly visualizing differences in ACO1 distribution between lesioned and normal tissues, directly demonstrating its tissue-specific expression pattern, and providing morphological evidence for pathological research of diseases.
- ELISA (Enzyme-Linked Immunosorbent Assay): The mainstream high-throughput quantitative technology. Based on the specific antigen-antibody binding principle, it accurately quantifies ACO1 protein concentrations in cells, serum and tissue samples via standard curves. It offers high detection sensitivity, manageable cost and high throughput, suitable for large-batch clinical sample screening and statistical analysis.
Advantages of Our ACO1 ELISA Kit:
- Sandwich ELISA format for accurate quantification of total ACO1 protein
- High sensitivity: 0.115 ng/mL; detection range: 0.312–20 ng/mL
- Compatible with serum/plasma, cell lysate, cell culture supernatant and tissue homogenate
- Intra-assay CV ＜10%, inter-assay CV ＜12%; stable results acceptable for journal publications
- Suitable for studies on ferroptosis, iron homeostasis, tumor metabolism, neurodegenerative diseases and fibrosis
- 48T / 96T detachable plates, ready-to-use upon opening, supporting high-throughput sample screening
3. Enzymatic activity assay: Precise characterization of functional activity
Distinct from simple protein quantification, enzymatic activity assays directly reflect the functional status of ACO1 and constitute a key technique for functional research. The coupled enzyme spectrophotometric method is widely used; ACO1 catalytic activity is precisely calculated by measuring the rate of absorbance change of NADH at 340 nm. In addition, native PAGE activity assay can be applied to simultaneously distinguish and measure the activities of cytosolic ACO1 and mitochondrial ACO2, pinpointing compartmentalized metabolic dysfunction in cells, which fits mechanistic research related to oxidative stress and iron metabolism disorders.
Conclusion
As a bifunctional hub governing cellular metabolism and iron homeostasis, ACO1 relies on its unique iron‑sulfur switch regulatory mechanism to interconnect multiple physiological pathways including energy metabolism, oxidative stress, apoptosis and vascular remodeling, serving as a critical molecule bridging physiological homeostasis and disease pathology. Aberrant expression and dysfunction of ACO1 are implicated in a wide spectrum of disorders such as tumors, neurodegenerative diseases, hematological diseases and fibrotic diseases, making it a disease biomarker and therapeutic target with great development potential. With continuous advances in detection technologies and progressive mechanistic research, ACO1 will undoubtedly exhibit broader application prospects in deciphering precise disease mechanisms, developing novel targeted therapeutics, and advancing precision clinical diagnosis and treatment.
I. Basic Information of ACO1: A Unique Bifunctional Hub Protein
ACO1 is a highly conserved functional gene encoded by the human genome, with Gene ID 48. Its aliases include IRP1, ACONS, IREBP1, etc. Localized in the cytoplasm, it represents the cytosolic isoform distinct from mitochondrial aconitase ACO2. It is widely expressed in various human tissues and cells, with markedly elevated expression in organs featuring vigorous metabolism and high iron demand.
In terms of molecular structure, ACO1 is a typical iron-sulfur protein whose core structure contains the critical [4Fe-4S] iron-sulfur cluster cofactor. This unique structure serves as the fundamental basis for its bifunctional switch. Unlike conventional monofunctional proteins, ACO1 does not undergo drastic fluctuations in expression level; instead, it switches functional modes merely via qualitative structural changes, acting as a core "switch" in physiological homeostasis regulation. The protein sequence of ACO1 is highly conserved throughout evolution, confirming its irreplaceable regulatory role in eukaryotic life activities.
Physiologically, ACO1 undertakes two core tasks: it functions as a metabolic enzyme participating in cellular energy cycling on one hand, and acts as a regulatory protein governing iron metabolic homeostasis on the other. These dual functions synergize and restrict each other to maintain normal cellular physiological status. Dysfunction directly leads to cellular metabolic disorders and pathological damage.
II. Mechanism of Action of ACO1: Precise Bifunctional Regulation Mediated by Iron-Sulfur Switch
The core regulatory logic of ACO1 lies in an iron-sulfur cluster-dependent functional switch mechanism. It can precisely sense intracellular iron concentration and oxidative stress status, dynamically toggling between the “metabolic enzyme form” and “gene regulatory protein form” without altering total protein abundance, thereby achieving fine-tuned regulation of cellular metabolism and iron homeostasis.
1. Iron-replete state: Exerts aconitase catalytic function
When intracellular iron levels are sufficient and the oxidative environment remains stable, ACO1 binds an intact [4Fe-4S] iron-sulfur cluster to form a fully active holoenzyme. In this state, it acts as a key enzyme in the tricarboxylic acid (TCA) cycle. It specifically catalyzes the isomerization of citrate into isocitrate to sustain continuous TCA cycle flux, supporting cellular glucose metabolism and energy production. Meanwhile, it promotes NADPH generation, preserves the reduced state of intracellular glutathione, mitigates oxidative stress damage, and maintains normal cellular proliferation and metabolic rhythm.
2. Iron-deficient / stress state: Switches to iron regulatory protein function
Under conditions of cellular iron deprivation, reactive oxygen species (ROS) accumulation or hypoxic stress, the [4Fe-4S] iron-sulfur cluster of ACO1 rapidly disassembles, triggering conformational changes in the protein. It loses enzymatic catalytic activity and converts into apoprotein (apoIRP1). The remodeled ACO1 acquires strong RNA-binding capacity and specifically binds to iron-responsive elements (IREs) on target mRNAs, modulating the expression of iron-metabolism-related genes via post-transcriptional regulation.
This regulation exhibits strict site specificity: binding to the 5′ untranslated region (5′UTR) of target mRNAs represses translation of ferritin, mitochondrial ACO2 and other proteins, reducing iron storage and mitochondrial metabolic consumption. Binding to the 3′ untranslated region (3′UTR) protects mRNAs of transferrin receptor 1 (TfR1) and divalent metal transporter 1 (DMT1) from degradation, facilitating iron uptake and transport. Through this mechanism, ACO1 rapidly boosts cellular iron acquisition, minimizes iron loss, restores cellular iron homeostasis, and adapts cellular metabolism under stress.
3. Coordinated regulation of downstream signaling pathways
Beyond core iron and energy metabolism control, ACO1 further modulates cellular physiology via extended axes including the ACO1–HIF-2α axis and ferroptosis pathway. By regulating the expression and activity of hypoxia-inducible factor HIF-2α, it participates in systemic oxygen sensing, erythropoiesis and vascular remodeling. As a critical upstream regulator of ferroptosis, it governs cellular iron overload and lipid peroxidation levels to determine the progression of programmed cell death, interconnecting a multi-layered regulatory network spanning metabolism, stress response and cell death.
III. Association of ACO1 with Diseases: A Key Regulatory Target for Multifarious Diseases
Dysfunction of ACO1 directly disrupts cellular iron homeostasis and energy metabolic balance, triggering a cascade of pathological alterations including oxidative stress, metabolic disorders and dysregulated apoptosis. It is extensively involved in the initiation and progression of multiple severe disorders such as tumors, neurodegenerative diseases, hematological diseases and fibrotic diseases, rendering it a highly promising diagnostic biomarker and therapeutic target.
1. Malignant tumors: Regulation of tumor proliferation and ferroptosis evasion
ACO1 exhibits specific downregulation in a variety of tumors. The decreased expression of ACO1 serves as a critical mechanism enabling tumor cells to evade ferroptosis and sustain unlimited proliferation. In malignancies including hepatocellular carcinoma, non‑small cell lung cancer and endometrial carcinoma, reduced ACO1 expression disturbs cellular iron metabolism and causes aberrant iron accumulation. Meanwhile, it suppresses iron‑dependent lipid peroxidation‑mediated programmed cell death, supporting tumor cell survival.
In addition, ACO1 modulates the tumor microenvironment via the HIF‑2α pathway. ACO1 depletion markedly increases HIF‑2α protein accumulation in tumor cells and activates oncogenic pathways such as c‑Myc and TGFα. This promotes tumor cell proliferation, invasion and metastasis, and mediates tumor angiogenesis to accelerate disease progression. Clinical studies have verified that ACO1 expression level is strongly correlated with tumor stage and prognosis; patients with low ACO1 expression carry a higher risk of recurrence and shorter survival time.
2. Neurodegenerative diseases: Mediation of brain iron accumulation and neuronal injury
Disrupted brain iron homeostasis represents a core pathological hallmark of neurodegenerative diseases, and ACO1 acts as the central protein governing brain iron metabolism. In disorders such as Parkinson’s disease and Huntington’s disease, ACO1 activity is abnormally elevated in patients’ brain tissues, which overactivates the expression of iron transporter DMT1 and leads to excessive iron deposition in critical brain regions including the substantia nigra and striatum.
Excessive iron buildup induces robust oxidative stress, reduces cerebral glutathione antioxidant capacity and triggers ferroptotic death of dopaminergic neurons. Meanwhile, aberrant ACO1 function suppresses the expression of mitochondrial ACO2 and impairs energy production in the tricarboxylic acid cycle, resulting in energy metabolism failure in neurons. Ultimately, this leads to degenerative neuronal damage and progressive clinical manifestations such as motor dysfunction and cognitive decline.
3. Hematological and cardiovascular diseases: Regulation of erythropoiesis and vascular homeostasis
The ACO1–HIF2α axis constitutes an essential regulatory pathway for hematological homeostasis. ACO1 gene defects or functional inactivation cause abnormal overexpression of renal HIF2α, which continuously stimulates massive secretion of erythropoietin (EPO) and leads to secondary polycythemia. Moreover, HIF2α activation in pulmonary endothelial cells upregulates endothelin 1 expression, inducing vasoconstriction, pulmonary hypertension and other cardiovascular lesions. Besides, in iron metabolic disorders during pregnancy, placental ACO1 dysfunction results in insufficient iron acquisition by the fetus and elevates the risk of iron‑deficiency anemia in newborns.
4. Fibrotic diseases: Involvement in tissue remodeling and disease progression
Studies on idiopathic pulmonary fibrosis confirm that aberrant ACO1 expression in pulmonary blood vessels is highly synchronized with fibrotic progression. Under pathological conditions with impaired mitochondrial metabolism, ACO1‑mediated cytoplasmic metabolic disturbance and iron homeostasis imbalance promote abnormal proliferation of pulmonary fibroblasts and excessive extracellular matrix deposition, accelerating the progression of pulmonary fibrosis. Thus, ACO1 acts as a valuable auxiliary biomarker for disease advancement of pulmonary fibrosis.
IV. ACO1 Detection Technology: A Precise System from Molecular Quantification to Activity Characterization
Accurate detection of ACO1 gene expression, protein abundance and enzymatic activity serves as core support for deciphering its physiological functions, linking pathological mechanisms of diseases and exploring its clinical translational value. At present, ACO1 detection has established a comprehensive technical system covering gene, protein and enzymatic activity levels, catering to diverse scenarios including basic research, clinical sample screening and target validation.
1. Gene-level detection: Nucleic acid quantification and mutation analysis
Quantitative real-time PCR (qRT-PCR) is the primary technique. Total RNA is extracted from cell or tissue samples, and target ACO1 fragments are amplified using specific primers to precisely quantify ACO1 mRNA expression levels. This method rapidly identifies aberrant fluctuations in ACO1 gene transcription in samples and is suitable for large-scale preliminary screening and differential analysis between disease and control groups. Combined with gene sequencing, it can detect ACO1 gene mutations and polymorphic loci, elucidate the mechanisms of functional defects caused by genetic variants, and provide evidence for tracing the etiology of hereditary iron metabolic disorders.
2. Protein-level detection: Qualitative localization and precise quantification
This represents the most commonly applied core dimension of ACO1 detection, with multiple well-established techniques available for different testing requirements:
- Western Blot (WB): Utilizes ACO1-specific antibodies for qualitative and semi-quantitative detection of ACO1 protein in samples. It reliably identifies differences in protein expression, featuring simple operation and high specificity, and is widely adopted to verify protein expression levels in basic research.
- Immunohistochemistry (IHC) / Immunofluorescence (ICC/IF): Enables tissue and cellular localization of ACO1 protein, clearly visualizing differences in ACO1 distribution between lesioned and normal tissues, directly demonstrating its tissue-specific expression pattern, and providing morphological evidence for pathological research of diseases.
- ELISA (Enzyme-Linked Immunosorbent Assay): The mainstream high-throughput quantitative technology. Based on the specific antigen-antibody binding principle, it accurately quantifies ACO1 protein concentrations in cells, serum and tissue samples via standard curves. It offers high detection sensitivity, manageable cost and high throughput, suitable for large-batch clinical sample screening and statistical analysis.
Advantages of Our ACO1 ELISA Kit:
- Sandwich ELISA format for accurate quantification of total ACO1 protein
- High sensitivity: 0.115 ng/mL; detection range: 0.312–20 ng/mL
- Compatible with serum/plasma, cell lysate, cell culture supernatant and tissue homogenate
- Intra-assay CV ＜10%, inter-assay CV ＜12%; stable results acceptable for journal publications
- Suitable for studies on ferroptosis, iron homeostasis, tumor metabolism, neurodegenerative diseases and fibrosis
- 48T / 96T detachable plates, ready-to-use upon opening, supporting high-throughput sample screening
3. Enzymatic activity assay: Precise characterization of functional activity
Distinct from simple protein quantification, enzymatic activity assays directly reflect the functional status of ACO1 and constitute a key technique for functional research. The coupled enzyme spectrophotometric method is widely used; ACO1 catalytic activity is precisely calculated by measuring the rate of absorbance change of NADH at 340 nm. In addition, native PAGE activity assay can be applied to simultaneously distinguish and measure the activities of cytosolic ACO1 and mitochondrial ACO2, pinpointing compartmentalized metabolic dysfunction in cells, which fits mechanistic research related to oxidative stress and iron metabolism disorders.
Conclusion
As a bifunctional hub governing cellular metabolism and iron homeostasis, ACO1 relies on its unique iron‑sulfur switch regulatory mechanism to interconnect multiple physiological pathways including energy metabolism, oxidative stress, apoptosis and vascular remodeling, serving as a critical molecule bridging physiological homeostasis and disease pathology. Aberrant expression and dysfunction of ACO1 are implicated in a wide spectrum of disorders such as tumors, neurodegenerative diseases, hematological diseases and fibrotic diseases, making it a disease biomarker and therapeutic target with great development potential. With continuous advances in detection technologies and progressive mechanistic research, ACO1 will undoubtedly exhibit broader application prospects in deciphering precise disease mechanisms, developing novel targeted therapeutics, and advancing precision clinical diagnosis and treatment.
