SLC28A3 encodes human concentrative nucleoside transporter 3 (hCNT3), a sodium-dependent transporter mediating uptake of both pyrimidine and purine nucleosides 12. The transporter operates via a 2:1 sodium/nucleoside symport mechanism and exhibits N3/cib transport characteristics, showing marked transport of thymidine and inosine 1. SLC28A3 transports endogenous nucleosides including uridine, adenosine, and cytidine, while also accepting clinically relevant nucleoside analogs such as gemcitabine, AZT, and ribavirin 134. A functionally relevant splice variant, hCNT3ins, localizes to the endoplasmic reticulum and participates in intracellular nucleoside salvage 5. Genetically, common coding variants in SLC28A3 are conserved in function 2, while intronic and synonymous variants (rs7853758, rs885004) associate with reduced anthracycline-induced cardiotoxicity in pediatric cancer patients 67. Mechanistically, SLC28A3 knockout protects cardiomyocytes against doxorubicin toxicity, and a novel cardioprotective variant (rs11140490) acts through regulation of antisense RNA SLC28A3-AS1 68. Clinical implications include pharmacogenomic testing recommendations for doxorubicin-treated children and potential therapeutic targeting through competitive inhibitors like desipramine 67. Additionally, SLC28A3 expression predicts fludarabine-cyclophosphamide response in chr9 lymphocytic leukemia and serves as a novel ductal cell marker in pancreatic islets 910.