The function of ENTPD8 (ectonucleoside triphosphate diphosphohydrolase 8, Ensembl gene identifier ENSG00000188833) is as follows. Canalicular ectonucleoside NTPDase responsible for the main hepatic NTPDase activity (PubMed:17095758). Catalyzes the hydrolysis of nucleoside triphosphates (NTPs) and diphosphates (NDPs) (PubMed:16752921, PubMed:17095758, PubMed:17603550). The enzyme sequentially removes phosphate groups in two successive steps, converting NTPs to nucleoside monophosphates (NMPs) via NDP intermediates (PubMed:16752921, PubMed:17095758, PubMed:17603550). This activity contributes to the regulation of extracellular levels of nucleotides (PubMed:16752921, PubMed:17095758, PubMed:17603550). Hydrolyzes ATP, UTP, ADP, and UDP and prefers triphosphonucleosides and adenine over uracil as substrates (PubMed:17095758). Does not hydrolyzes AMP (PubMed:17095758). {ECO:0000269|PubMed:16752921, ECO:0000269|PubMed:17095758, ECO:0000269|PubMed:17603550}.