PLA2G2F is a secretory, calcium-dependent phospholipase A2 that hydrolyzes extracellular phospholipids at the sn-2 position, with preferential catalytic efficiency for phosphatidylglycerols and phosphatidylethanolamines 1. Expressed in suprabasal epidermis, PLA2G2F regulates skin homeostasis by generating bioactive lipid mediators, particularly ethanolamine lysoplasmalogen (P-LPE) and protectin D1, distinct from canonical arachidonate metabolites 2. PLA2G2F is central to psoriasis pathogenesis: Pla2g2f-deficient mice are protected from psoriasis, contact dermatitis, and skin cancer, while overexpression promotes psoriasis-like hyperplasia 2. The sPLA2-IIF/P-LPE axis promotes keratinocyte proliferation and Th17 immune responses; enzymatic degradation of P-LPE by lysophospholipase D attenuates psoriatic inflammation in both murine and human systems 3. PLA2G2F is part of a shared pathogenic phospholipase pathway in psoriasis and pityriasis rubra pilaris, regulating eicosanoid mobilization and epidermal barrier homeostasis 4. Genetic polymorphisms in PLA2G2F influence plasma triglyceride responses to omega-3 PUFA supplementation 5. Additionally, PLA2G2F expression is altered in nifedipine-induced gingival overgrowth and ZIKV-infected neural cells, suggesting roles in drug-induced pathology and viral infection responses 6, 7.