Glycerophosphocholine cholinephosphodiesterase (ENPP6)

Glycerophosphocholine cholinephosphodiesterase (ENPP6) is a choline-specific ectoenzyme from the ectonucleotide pyrophosphatase/phosphodiesterase (ENPP) family that is anchored to the cell membrane via a glycosylphosphatidylinositol (GPI) moiety[1][2]. It hydrolyzes choline-containing lysophospholipids—primarily glycerophosphocholine (GPC), lysophosphatidylcholine (LPC), sphingosylphosphorylcholine (SPC), platelet-activating factor (PAF), and lysoPAF—producing phosphocholine[1][2][3]. ENPP6 is highly expressed in the myelin sheath of oligodendrocytes in the central nervous system and in liver sinusoidal endothelial cells and the renal proximal tubule, playing an essential role in supplying choline for phospholipid synthesis and cellular function[2]. Knockout of ENPP6 leads to impaired myelination and a fatty liver phenotype, identifying it as a critical enzyme in choline metabolism and a potential early biomarker for oligodendrocyte differentiation and myelin integrity[2]. No drugs or inhibitors are currently reported for direct modulation of ENPP6 in clinical settings. Key notes: - Considered a validated biochemical target and potential biomarker based on known biology. - Functions as an enzyme, not a receptor or transporter. - No clinical drugs described; no established mechanism-of-action category for approved or experimental therapeutics. - Dysfunction may be associated with neurological or metabolic disorders due to its key role in choline supply for myelin and hepatocyte function[2].

Other names

Ectonucleotide pyrophosphatase/phosphodiesterase 6GPC-CpdeE-NPP 6NPP-6MGC33971Choline-specific glycerophosphodiester phosphodiesteraseB830047L21Rik