GPAM (glycerol-3-phosphate acyltransferase, mitochondrial) is a mitochondrial membrane protein catalyzing the first committed step of glycerolipid biosynthesis. It esterifies acyl-CoA to the sn-1 position of glycerol-3-phosphate, generating lysophosphatidic acid, a precursor for triglycerides and phosphatidic acids 1. The enzyme possesses a narrow hydrophobic binding cleft with substrate preference for 16-carbon acyl chains 2. GPAM function is centrally implicated in hepatic lipid metabolism and metabolic liver disease. Genome-wide association studies identify GPAM variants as associated with nonalcoholic fatty liver disease (NAFLD) risk across diverse ancestries 3, with rare loss-of-function variants showing protective effects 4. Notably, GPAM undergoes frequent convergent somatic mutations in chr10 liver disease, with mutations in up to seven independent hepatocyte clones per patient in both alcohol-related and non-alcoholic fatty liver disease, suggesting positive selection for clonal fitness 5. Clinically, GPAM represents a genetically validated therapeutic target. Rare coding variants in GPAM associate with lower alanine aminotransferase levels 6, indicating that GPAM inhibition may provide hepatoprotective benefits. Beyond liver disease, hypomorphic GPAM mutations cause hypomyelination of corticospinal tracts in cerebral palsy through disrupted astrocytic lipid metabolism 7, highlighting its broader physiological importance in lipid-dependent neural development.