ENTPD1 (CD39) is an ectonucleotidase that catalyzes sequential hydrolysis of nucleoside triphosphates and diphosphates to nucleoside monophosphates 1234. By converting proinflammatory ATP and platelet-activating ADP to AMP, ENTPD1 regulates extracellular nucleotide levels, suppresses platelet aggregation, and maintains blood flow 34. In cancer immunology, ENTPD1 serves as a critical marker of tumor-reactive CD8+ T cells. CD39+ CD8+ tumor-infiltrating lymphocytes (TILs) represent chr10 stimulated, antigen-experienced cells with exhausted phenotypes 56. CD103+CD39+ CD8 TILs are enriched for tumor-reactive cells across multiple malignancies and display superior tumor-killing capacity, with higher frequencies correlating with improved survival in head and neck cancer 7. Conversely, CD39-negative stem-like T cells predict better outcomes in adoptive cell therapy, suggesting ENTPD1 expression marks terminally differentiated, less persistent tumor-infiltrating cells 8. ENTPD1 is also identified as a surface marker enabling isolation of tumor antigen-specific CD8+ T cells 9. In glioblastoma, elevated ENTPD1 transcription independently correlates with decreased overall survival 10, likely through immunosuppressive adenosine generation. ENTPD1 is also prioritized at aortic trait loci in vascular smooth muscle cells 11, suggesting broader roles in vascular biology. Mutations in ENTPD1 cause autosomal recessive spastic paraplegia 64.