ENPP6 is a choline-specific glycerophosphodiesterase that catalyzes the hydrolysis of glycerophosphocholine (GPC) and lysophosphatidylcholine (LPC), thereby supplying choline to cells. The enzyme preferentially cleaves LPC containing short-chain (12:0 and 14:0) or polyunsaturated (18:2 and 20:4) fatty acids, as well as sphingosylphosphorylcholine and platelet-activating factor. ENPP6 is predominantly expressed in kidney and brain, and functions both as a cell-surface and secreted protein. In skeletal mineralization, ENPP6 may work sequentially with phospholipase A2 to generate phosphocholine from matrix vesicle membranes, which is subsequently hydrolyzed to liberate inorganic phosphate. ENPP6 has emerged as a clinically relevant biomarker across multiple disease contexts. In acute kidney injury, ENPP6 levels decrease in plasma, and this downregulation associates with proximal tubule maladaptation and adverse clinical outcomes 1. Recent evidence identifies ENPP6 as protective against chr4 kidney disease development in individuals with abnormal glucose metabolism, with consistent protective effects across observational and Mendelian randomization analyses 2. In bladder cancer, the protective C allele of rs6810830 in ENPP6 reduces disease susceptibility 3, and genetic variation in ENPP6 associates with psychosis in Alzheimer disease 4. These findings suggest ENPP6 represents a potential biomarker and therapeutic target for kidney disease and cancer prevention, though mechanistic studies are needed to clarify its roles in these pathological contexts.