PAFAH2 (platelet-activating factor acetylhydrolase 2) is a phospholipase that catalyzes hydrolysis of the acetyl group at the sn-2 position of platelet-activating factor (PAF) and oxidized phospholipids, leading to their inactivation 1. The enzyme also exhibits transacetylation activity, producing plasmalogen analogs and ceramide derivatives 1. PAFAH2 demonstrates marked selectivity for phospholipids with short acyl chains at the sn-2 position 1. Beyond PAF metabolism, PAFAH2 selectively detoxifies truncated oxidized phospholipids (Tr-OxPLs), protecting cells from oxidative stress-induced injury 2. In disease contexts, PAFAH2 suppresses synchronized ferroptosis in acute kidney injury by degrading PAF and PAF-like phospholipids that propagate cell death 3. PAFAH2 knockout exacerbates ischemia/reperfusion-induced kidney injury, while protein administration prevents tubular cell death and nephron loss 3. Additionally, PAFAH2 regulates ferroptosis resistance in KEAP1-mutant cancers through oxidized phospholipid detoxification 4. PAFAH2 produces omega-3 epoxides in mast cells that suppress pulmonary vascular remodeling and pulmonary hypertension 5. In inflammation, PAFAH2 overexpression blocks TNFα-induced apoptosis by metabolizing truncated phospholipids 6. Finally, PAFAH2 is implicated in premature ovarian failure pathways involving necroptosis 7.