Objective:

To synthesize current knowledge of ORM2 molecular biology and functional repertoire, critically appraise evidence linking ORM2 dysregulation to T2DM and CAD, evaluate ORM2 as a clinical biomarker and therapeutic target, and propose future research directions.

Approach:

• Link to T2DM and CAD: Reduced ORM2 expression is observed in obesity and insulin resistance, with associations to diabetic nephropathy and increased risk of myocardial infarction.

Key Findings:

• ORM2 suppresses hepatic de novo lipogenesis through AMPK signaling.
• ORM2 improves glucose homeostasis by modulating IFN-γ/STAT1 signaling in adipose tissue.
• Circulating ORM2 levels are linked to diabetic nephropathy and increased risk of myocardial infarction.
• Recombinant ORM2 has been shown to attenuate atherosclerosis and hepatic steatosis in preclinical models.

Interpretation:

ORM2 may mediate the relationship between metabolic dysfunction and vascular inflammation in T2DM and CAD.

Limitations:

• Insufficient characterization of ORM2 as a mechanistic bridge between metabolic dysfunction and coronary vascular inflammation.
• Need for more prospective clinical studies and Mendelian randomization analyses to clarify ORM2's role.

Conclusion:

ORM2 is a potential biomarker and therapeutic target within the adipose–liver–vascular axis, necessitating further investigation.