ENPP6 (ectonucleotide pyrophosphatase/phosphodiesterase 6) is a choline-specific glycerophosphodiesterase that plays crucial roles in choline metabolism and cellular signaling. The enzyme hydrolyzes glycerophosphocholine (GPC) and lysophosphatidylcholine (LPC) to supply choline to cells, with preference for LPC containing short or polyunsaturated fatty acids 1. ENPP6 also hydrolyzes other choline-containing lysophospholipids including sphingosylphosphorylcholine, platelet-activating factor, and lysoPAF 1. Beyond choline metabolism, ENPP6 contributes to skeletal mineralization by acting with PLA2 to generate phosphocholine from phosphatidylcholine in matrix vesicle membranes, which PHOSPHO1 can then hydrolyze to liberate inorganic phosphate for hydroxyapatite precipitation 2. The enzyme represents part of alternative 2-arachidonoylglycerol synthesis pathways (AlterAG-3), converting extracellular lysophospholipids into the endocannabinoid 2-AG through ectocellular cleavage 3. Clinically, ENPP6 shows protective associations with chr4 kidney disease in individuals with abnormal glucose metabolism 4 and serves as a biomarker for proximal tubule maladaptation following acute kidney injury 5. Genetic variants in ENPP6 are associated with bladder cancer susceptibility and Alzheimer's disease with psychosis 67.