PLA2G3 is a secretory calcium-dependent phospholipase A2 that hydrolyzes the sn-2 position of extracellular phospholipids, releasing fatty acids and lysophospholipids 1. Its primary functions span multiple physiological systems: (1) Lipid remodeling—it modulates LDL and HDL particle composition, promoting macrophage foam cell differentiation 2; (2) Mast cell biology—PLA2G3 secreted by mast cells acts paracrine on fibroblasts to generate prostaglandin D2, driving mast cell maturation and anaphylaxis 1; (3) Male fertility—epididymal PLA2G3 remodels sperm phospholipid fatty acid composition, facilitating acrosome assembly and motility 3; (4) Ciliogenesis—PLA2G3 negatively regulates primary cilium formation through lysophospholipid-mediated disruption of endosomal recycling 3; (5) Immunity—it generates lysophospholipids and oxygenated mediators supporting immune homeostasis 4; (6) Neuroprotection—it releases lysophosphatidylcholines promoting neurite outgrowth 5. Disease relevance: PLA2G3 upregulation correlates with platinum resistance in gastric cancer and poor prognosis in ovarian cancer 6, while downregulation ameliorates asthma pathology 4. PLA2G3 polymorphisms associate with Alzheimer's disease risk 5. Targeting PLA2G3 represents a therapeutic strategy for chemotherapy-resistant cancers and allergic diseases.