GPAT4 is an endoplasmic reticulum-localized glycerol-3-phosphate acyltransferase that catalyzes the rate-limiting first step in glycerolipid synthesis by converting glycerol-3-phosphate to lysophosphatidic acid 1. The enzyme accepts both saturated and unsaturated long-chain fatty acyl-CoAs as substrates 2 and is regulated through insulin-stimulated phosphorylation at serine and threonine residues, which increases its activity 3. GPAT4's catalytic activity critically depends on binding calcineurin B homologous protein 1 (CHP1), which stabilizes the enzyme and mediates its N-myristoylation—an essential modification for optimal activity and localization to lipid droplets 45. Key substrate recognition involves residue R427, which forms a salt bridge with glycerol-3-phosphate 6. In disease contexts, GPAT4 plays distinct roles: it protects cells against lipotoxicity 7 but also supports glycerophospholipid accumulation that promotes autophagy and colorectal cancer progression 8. GPAT4 expression is higher in radioresistant glioblastoma cells, correlating with larger lipid droplet formation 9. These findings establish GPAT4 as a central regulator of lipid metabolism with implications for metabolic diseases and cancer.