PLA2G10 encodes a secretory calcium-dependent phospholipase A2 that primarily hydrolyzes extracellular phospholipids, showing preference for phosphatidylcholines and releasing polyunsaturated fatty acids 1. The enzyme contributes to lipoprotein remodeling and hydrolyzes platelet activating factor in oxidized LDL 12. PLA2G10 demonstrates significant roles in cancer biology, where upregulation impairs T cell infiltration into tumors by hydrolyzing phospholipids into metabolites that inhibit chemokine-mediated T cell mobility, leading to immunotherapy resistance 3. In lung adenocarcinoma, tumor-derived PLA2G10 promotes progression by secreting arachidonic acid, which suppresses CD4+ T cell activation through inhibition of LCK and ZAP70 phosphorylation 4. PLA2G10 facilitates cell cycle progression in soft tissue leiomyosarcoma by elevating cyclin E1/CDK2 expression, with enzymatic activity being crucial for oncogenic properties 5. Paradoxically, in atherosclerosis, PLA2G10 appears protective, as deficiency in bone marrow cells doubles plaque size and increases necrotic cores, suggesting control of proatherogenic Th1 responses 6. The enzyme also influences gut microbiota and systemic metabolism, orchestrating omega-3 PUFA-SCFA interactions that affect obesity and insulin resistance 7. PLA2G10 serves as a potential biomarker, with elevated levels in serum exosomes correlating with aggressive NSCLC features and poor prognosis 8.