PLA2G2A encodes a secretory calcium-dependent phospholipase A2 that hydrolyzes phospholipids at the sn-2 position, with preference for phosphatidylethanolamines and phosphatidylglycerols over phosphatidylcholines. This enzyme plays multifaceted roles in inflammation, tissue repair, and disease progression. In breast cancer, PLA2G2A+ cancer-associated fibroblasts promote immune infiltration in HER2+ patients 1. The protein contributes to inflammatory responses in bullous pemphigoid through IL13-mediated immune-stromal crosstalk, where fibroblasts expressing IL13RA1 upregulate PLA2G2A in response to Th2 cell-derived IL13, amplifying pathogenic autoantibody production 2. In cardiovascular disease, PLA2G2A expression in fibroblasts promotes early carotid atherosclerosis progression through complement and coagulation cascade activation in macrophages 3. The enzyme also functions as a tumor suppressor in cholangiocarcinoma, where its expression is epigenetically silenced through STUB1-mediated UHRF1 ubiquitination and subsequent DNA hypermethylation 4. Additionally, PLA2G2A serves as a downstream effector in ferroptosis regulation, being upregulated when SELENOI deficiency disrupts ether lipid homeostasis, contributing to excessive lipid peroxidation in colitis and colorectal cancer 5. These findings highlight PLA2G2A's context-dependent roles in both promoting and suppressing disease processes across different tissues.