ENPP6 is a choline-specific glycerophosphodiester phosphodiesterase, which hydrolyzes the classical substrate for phospholipase C, p-nitrophenyl phosphorylcholine, while it does not hydrolyze the classical nucleotide phosphodiesterase substrate, p-nitrophenyl thymidine 5 prime-monophosphate. It hydrolyzes lysophosphatidylcholine (LPC) to form monoacylglycerol and phosphorylcholine but not lysophosphatidic acid, showing it has a lysophospholipase C activity. ENPP6 has a preference for LPC with short (12:0 and 14:0) or polyunsaturated (18:2 and 20:4) fatty acids. ENPP6 also hydrolyzes glycerophosphorylcholine and sphingosylphosphorylcholine efficiently. ENPP6 is predominantly expressed in kidney and brain.
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