PLA2G2E is a secreted, calcium-dependent phospholipase A2 that hydrolyzes the sn-2 ester bonds of extracellular phospholipids, primarily releasing unsaturated fatty acids and lysophosphatidylethanolamines 123. The enzyme preferentially targets bacterial membrane phospholipids (phosphatidylglycerols and phosphatidylethanolamines) and minor lipoprotein phospholipids, contributing to lipid remodeling and pathogen clearance 2. In response to high-fat diet, PLA2G2E moderately facilitates lipid accumulation in adipose tissue and liver while generating arachidonate precursors for prostaglandins and leukotrienes 4. The enzyme also functions in hair follicle homeostasis through selective release of lysophosphatidylethanolamines in skin. Clinically, PLA2G2E is implicated in multiple disease contexts: it promotes brain-autonomous neural repair after ischemic stroke by generating dihomo-γ-linolenic acid (DGLA) and its metabolite 15-HETrE, which induce neuroprotective transcriptional programs 56. During influenza infection, PLA2G2E regulates T cell-mediated immunity and viral clearance 7. Elevated serum PLA2G2E associates with neutrophilic asthma phenotypes 8, and genetic variants near PLA2G2E link to ulcerative colitis susceptibility 9, suggesting roles in inflammatory intestinal and pulmonary diseases.