Ectonucleoside triphosphate diphosphohydrolase 1

ENTPD1 (ectonucleoside triphosphate diphosphohydrolase 1) is a nucleotidase enzyme that catalyzes sequential hydrolysis of nucleoside triphosphates and diphosphates to nucleoside monophosphates (UniProt: P49961). By degrading extracellular ATP and ADP, it regulates nucleotide levels and suppresses platelet aggregation, thereby supporting vascular homeostasis (UniProt: P49961).

ENTPD1 is primarily expressed on the cell surface and in immune cells, where its nucleotide-degrading activity modulates inflammatory signaling. Pathogenic variants in ENTPD1 are associated with spastic paraplegia 64 (SPG64), a neurodegenerative disorder affecting lower-limb motor neurons (UniProt: P49961).

ENTPD1 is upregulated in Alzheimer's disease brain tissue relative to age-matched controls (Chaparral AD proteomics). Analysis of post-mortem AD brain samples by TMT-labeled proteomics revealed a mean log2 fold-change of +0.59 across measured subcellular fractions, suggesting that elevated ENTPD1 expression or accumulation may be relevant to AD pathology (Chaparral AD proteomics).