PLA2G12A encodes a secreted phospholipase A2 group XIIA that catalyzes calcium-dependent hydrolysis of 2-acyl groups in phosphoglycerides 1. While enzymatic activity was traditionally considered its primary function, recent evidence indicates PLA2G12A operates through non-enzymatic mechanisms in metabolic regulation. Hepatic overexpression of PLA2G12A protects against diet-induced obesity and insulin resistance by increasing energy expenditure and physical activity, independent of catalytic activity 1. The mechanism involves upregulation of ApoC2 and Cd36, enhancing triglyceride clearance and hepatic fatty acid uptake 1. Genome-wide association studies identified PLA2G12A as an insulin resistance locus that improves insulin sensitivity through arachidonic acid liberation 2. Clinically, PLA2G12A represents a novel therapeutic target for metabolic diseases. Low PLA2G12A expression serves as a prognostic biomarker in colorectal cancer, correlating with poor recurrence-free and overall survival; PLA2G12A deficiency promotes cancer cell proliferation, migration, and invasion 3. It functions as a lipid-related diagnostic biomarker for acute myocardial infarction, identified through machine learning analysis of lipid metabolism genes 4. Additionally, PLA2G12A polymorphisms influence schizophrenia susceptibility in Han Chinese populations 56, and rs2285714 shows suggestive association with anti-VEGF treatment response in macular degeneration 7.