PLA2G4E (phospholipase A2 group IVE) is a calcium-dependent N-acyltransferase primarily functioning in the brain to catalyze biosynthesis of N-acyl ethanolamines (NAEs) 1. The enzyme transfers fatty acyl chains from phosphatidylcholine to phosphatidylethanolamine, generating N-acyl phosphatidylethanolamine (NAPE) and related precursors of bioactive molecules like anandamide 12. Beyond lipid metabolism, PLA2G4E regulates intracellular membrane trafficking and endocytic recycling through modulation of membrane curvature 3. PLA2G4E exhibits tissue-specific expression patterns and responds to calcium influx, with emerging roles in metabolic homeostasis, neuronal signaling, and stress adaptation 3. In Alzheimer's disease, decreased PLA2G4E expression in late-stage patients correlates with cognitive decline; viral-mediated overexpression restored cognitive deficits in APP/PS1 mice by promoting dendritic spine development, independent of amyloid-tau pathology 4. In psoriasis, PLA2G4E-derived NAEs provide counter-regulatory anti-inflammatory effects in keratinocytes 5. Additionally, PLA2G4E inhibition reduces lysosomal membrane permeabilization-induced necroptosis, promoting skin flap survival in ischemic conditions 6. Preliminary evidence associates rare variants with panic disorder risk and severe pediatric sepsis phenotypes 78, suggesting broader clinical relevance beyond neurodegeneration.