Ectonucleoside triphosphate diphosphohydrolase 8 (ENTPD8)

Ectonucleoside triphosphate diphosphohydrolase 8 (ENTPD8) is a membrane-bound ectonucleotidase enzyme that catalyzes the hydrolysis of extracellular nucleoside triphosphates (e.g., ATP, UTP) and diphosphates (ADP, UDP), thereby controlling nucleotide concentrations in diverse tissues[1][3]. ENTPD8 is highly expressed in liver canalicular membranes and epithelial cells in the intestine, playing a key role in hepatic and intestinal purine homeostasis[3][4]. Its activity modulates purinergic signaling, impacting immune responses, cellular proliferation, migration, and apoptosis. In cancer, particularly hepatocellular carcinoma, ENTPD8 suppresses tumor cell proliferation and invasion and regulates PD-L1 expression, with enhanced anti-tumor efficacy observed when combined with PD-L1 blockade[2]. In the gut, ENTPD8 prevents excessive inflammation by metabolizing luminal ATP released from commensal bacteria, protecting against colitis via metabolic control of myeloid cells and reduction of innate immune pathology[4]. Pathological dysregulation or deficiency of ENTPD8 activity is linked to heightened inflammation, immune dysfunction, and associations with specific genetic disorders such as tick paralysis and spastic paraplegia[1]. While not directly targeted by approved drugs, ENTPD8 is emerging as a potential therapeutic target and biomarker in cancer and inflammatory diseases.

Other names

E-NTPDase 8NTPDase 8NTPDase8UNQ2492NTPDase-8GLSR2492liver ecto-ATP-diphosphohydrolasecanalicular ecto-ATPase

Hydrolysis of extracellular nucleotides, reducing ATP/ADP/UTP/UDP levels; Modulation of PD-L1 expression via miR-214-5p pathway[2]; Inhibition of proinflammatory glycolytic reprogramming in myeloid cells through control of ATP levels and P2X4 receptor signaling[4]