CD39 (Ectonucleoside triphosphate diphosphohydrolase-1, encoded by the ENTPD1 gene) is an ectoenzyme that hydrolyzes extracellular ATP into AMP, serving as the rate-limiting enzyme in the generation of adenosine. In the tumor microenvironment, CD39 works in concert with CD73 to ultimately produce immunosuppressive adenosine, which inhibits antitumor immune responses. CD39 is widely expressed on the surface of various immune cells, including T cells, B cells, natural killer cells, dendritic cells, and macrophages. Due to its critical role in immune suppression, CD39 has emerged as a promising target for cancer immunotherapy, with several inhibitors and antibody drugs currently under clinical investigation.