PLA2G2E is a secreted, calcium-dependent phospholipase A2 that hydrolyzes the sn-2 ester bond of extracellular phospholipids, releasing unsaturated fatty acids and lysophospholipids. It preferentially cleaves phosphatidylserines, phosphatidylinositols, and phosphatidylglycerols—the major phospholipid components of bacterial membranes—making it important for pathogen clearance. The enzyme also modulates arachidonate availability, a precursor for prostaglandins and leukotrienes, thereby influencing inflammatory and allergic responses. Recent evidence reveals roles in neurological recovery and viral immunity. Following ischemic stroke, neuronal PLA2G2E generates dihomo-γ-linolenic acid (DGLA), which is metabolized to 15-hydroxy-eicosatrienoic acid (15-HETrE), a lipid mediator that induces peptidyl arginine deiminase 4 to promote neural repair 1. During influenza infection, PLA2G2E regulates T cell-mediated antiviral immunity; Pla2g2e-deficient mice show reduced survival and higher viral loads, with impaired cellular immunity 2. In metabolic contexts, PLA2G2E modestly facilitates lipid accumulation in adipose tissue and liver during high-fat feeding 3. Genome-wide association studies identify PLA2G2E variants near the RNF186-OTUD3 locus as associated with ulcerative colitis susceptibility across ethnic populations 4. The enzyme is also implicated in asthma pathogenesis as a serum biomarker for neutrophilic asthma phenotypes 5.