AGPAT3 (1-acylglycerol-3-phosphate O-acyltransferase 3) catalyzes the conversion of lysophosphatidic acid (LPA) to phosphatidic acid (PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone 1. The enzyme acts on LPA containing saturated or unsaturated fatty acids (C16:0-C20:4) and preferentially uses arachidonoyl-CoA as an acyl donor, with additional activity toward lysophospholipids 1. AGPAT3 is essential for phosphatidic acid and glycerophospholipid biosynthesis, critical processes for membrane biogenesis and lipid storage 2. Mechanistically, AGPAT3 functions in lipid remodeling pathways with disease-relevant consequences. IFN-γ signaling upregulates AGPAT3 expression via IRF1, driving accumulation of polyunsaturated ether phospholipids that sensitize tumor cells to ferroptosis and enhance immunotherapy efficacy 3. Conversely, UBXD8 activation of AGPAT3 specifically incorporates docosahexaenoate (DHA) into phospholipids; excess unsaturated fatty acids disrupt this complex, preventing pathological DHA accumulation and ferroptosis 4. In breast cancer, AGPAT3-dependent lipid peroxidation promotes ferroptosis vulnerability to CDK4/6 inhibition 5. Loss-of-function mutations cause severe phenotypes: biallelic AGPAT3 variants underlie intellectual disability with retinitis pigmentosa (IDRP) syndrome through impaired neuronal migration 6. AGPAT3 knockout mice exhibit reduced adipose tissue mass with impaired adipocyte differentiation, though maintaining normal glucose homeostasis 7. AGPAT3 genetic variants associate with milk fatty acid composition in dairy cattle 8.