Members of the ecto-nucleoside triphosphate diphosphohydrolase (eNTPDase) protein family are glycosylated enzymes that hydrolyze nucleoside 5’-triphosphates and 5’-diphosphates in extracellcular space. The enzymatic activities of eNTPDase are dependent on cations such as magnesium and calcium. Members of this protein family differ in their affinities for triphosphates versus diphosphates as substrate material. NTPDase8, also known as ENTPD8 (ectonucleoside triphosphate diphosphohydrolase 8) or E-NTPDase 8, is a 495 amino acid multi-pass membrane protein belonging to the GDA1/CD39 NTPase family. As a canalicular ectonucleoside NTPDase, NTPDase8 is involved in hepatic NTPDase activity and helps concentrate extracellular nucleotides. NTPDase8 binds calcium as a cofactor, becomes glycosylated following translation and exists as two alternatively spliced isoforms.