PLA2G4A (phospholipase A2 group IVA) is a calcium-dependent enzyme that plays critical roles in membrane lipid remodeling, inflammatory signaling, and cellular stress responses. The enzyme primarily hydrolyzes phospholipids at the sn-2 position to release arachidonic acid, serving as a key precursor for eicosanoid biosynthesis including prostaglandins and leukotrienes 1. PLA2G4A demonstrates significant pathological involvement in neurological disorders, where its activation leads to lysosomal membrane permeabilization (LMP), autophagy dysfunction, and neuronal death following traumatic brain injury and ischemic stroke 23. The enzyme's dysregulation contributes to necroptosis in tissue ischemia through LMP-mediated cellular damage 4. In reproductive biology, PLA2G4A is essential for decidual macrophage function and pregnancy maintenance, with defective lysophosphatidic acid-autophagy signaling increasing miscarriage risk 5. Clinically, PLA2G4A serves as a biomarker for diabetic kidney disease progression and platinum resistance in gastric cancer, where it modulates glycerophospholipid metabolism 67. The enzyme also shows promise as a therapeutic target in non-small cell lung cancer, where its expression correlates with treatment resistance and poor prognosis 8. These findings establish PLA2G4A as a central regulator of cellular metabolism and stress responses with significant therapeutic implications.