SERPINA3 is a serine protease inhibitor with pleiotropic functions in cardiovascular and neurological systems. Biochemically, SERPINA3 inhibits neutrophil cathepsin G and mast cell chymase, which regulate angiotensin-2 activation, though its primary physiological role remains incompletely understood. In cardiac pathology, SERPINA3 is abundantly expressed in cardiac fibroblasts and protects against ischemia-reperfusion injury in a lactylation-dependent manner by suppressing cardiomyocyte apoptosis through RISK and SAFE pathway activation 1. Post-myocardial infarction, SERPINA3 regulates extracellular matrix remodeling by inhibiting proteolytic activity, and genetic deletion impairs cardiac function through increased matrix degradation and adverse myocyte hypertrophy 2. In the central nervous system, SERPINA3 expression is dysregulated across multiple neurological conditions and serves as a disease-associated oligodendrocyte marker correlating with cognitive decline in Alzheimer's disease 3. However, its precise role in CNS pathology remains controversial—whether SERPINA3 induction represents protective or pathogenic mechanisms may depend on cellular source and disease context 4. Clinically, SERPINA3 levels associate with myocardial infarction outcomes and function as a biomarker in neurosyphilis, glaucoma, and multiple sclerosis 56. These findings suggest SERPINA3 is a context-dependent regulator of tissue remodeling and inflammation with significant translational potential.