The Phospholipase A2 Superfamily in Health and Disease: From Lipid Signaling to Inflammation, Cancer, and Neurodegeneration.

The phospholipase A2 (PLA2) superfamily comprises more than 50 enzymes that differ markedly in structure, catalytic mechanisms, and biological functions. Although all members share the ability to cleave acyl chains from membrane glycerophospholipids, many PLA2 enzymes catalyze additional reactions that influence membrane composition, lipid signaling, and cellular homeostasis. Through these activities, PLA2 enzymes contribute to the generation of free fatty acids, lysophospholipids, and downstream lipid mediators and participate in a wide range of physiological processes. Dysregulation of PLA2 activity has been associated with numerous pathological conditions, including inflammation, cancer, metabolic dysfunction, neurodegeneration, and tissue injury. This review summarizes the major PLA2 families, outlines their structural and biochemical features, and highlights emerging insights into their roles in health and disease.