ENPP7 (ectonucleotide pyrophosphatase/phosphodiesterase 7) is a choline-specific phosphodiesterase that functions primarily as an intestinal alkaline sphingomyelinase 1. Its principal role is hydrolyzing sphingomyelin into ceramide and phosphocholine, thereby facilitating sphingomyelin digestion and fatty acid absorption in the gastrointestinal tract 1. Beyond sphingomyelin catabolism, ENPP7 possesses phospholipase C activity that cleaves phosphocholine from platelet-activating factor (PAF) and palmitoyl lysophosphatidylcholine, inactivating the pro-inflammatory mediator PAF 2. Mechanistically, ENPP7 recognizes substrates through an NPP7-specific aromatic box of tyrosine residues and requires bile salts for optimal activity 1. The enzyme contains conserved metal-binding sites essential for PAF hydrolysis 2. Clinically, ENPP7 dysregulation associates with disease pathology: bile ENPP7 activity is significantly reduced in cholangiocarcinoma and other malignancies 3, while intestinal ENPP7 downregulation correlates with inflammatory bowel disease and increased cancer risk 4. Enhanced sphingolipid metabolism involving ENPP7 upregulation promotes thrombosis through inflammation exacerbation in deep vein thrombosis patients with coronary heart disease 5. Conversely, ENPP7 expression increases with probiotic interventions, supporting beneficial digestive and metabolic effects 6. These findings position ENPP7 as a key regulator of intestinal lipid metabolism with protective anti-inflammatory potential.