Ectonucleoside triphosphate diphosphohydrolase 5 (ENTPD5)

Ectonucleoside triphosphate diphosphohydrolase 5 (ENTPD5) is an enzyme located primarily in the endoplasmic reticulum, where it hydrolyzes nucleoside diphosphates—particularly GDP, IDP, and UDP—into monophosphates. ENTPD5 plays a crucial role in the regulation of protein N-glycosylation and ER homeostasis by producing UMP, needed for proper glycoprotein folding and function. It is essential for physiological processes such as skeletal mineralization by maintaining the local balance of phosphate and pyrophosphate, and it acts as a key modulator of ER stress responses and cell fate by promoting proliferation or inhibiting apoptosis, particularly in renal tubules and tumor cells. In disease, ENTPD5 is implicated as a driver of cancer progression through its metabolic roles and as a regulator of diabetic kidney disease and bone development by controlling ER stress and mineralization pathways.

Other names

Nucleoside diphosphate phosphatase ENTPD5CD39L4PCPHNTPDase 5GDPase ENTPD5UDPase ENTPD5NTPDase-5CD39 antigen-like 4ER-UDPaseGuanosine-diphosphatase ENTPD5Inosine diphosphate phosphatase ENTPD5Proto-oncogene CPHPcph proto-oncogene proteinUridine-diphosphatase ENTPD5

Targeting ENTPD5 may modulate ER stress and cell death via control of protein N-glycosylation and nucleotide metabolism. Inhibition could affect tumor energy metabolism and proliferation.