Slc29a1, also known as equilibrative nucleoside transporter 1 (ENT1), is a crucial gene encoding a cell membrane transporter. It drives cellular nicotinamide uptake, thereby establishing nicotinamide metabolism homeostasis. It also plays a role in regulating cellular respiration and senescence by altering the NAD+ pool level and mitochondrial status [1]. Additionally, it is involved in the transportation of nucleoside analogs like cytosine arabinoside (AraC) and ribavirin, which are important in cancer treatment and anti-HCV therapy respectively [2,3].

In acute myeloid leukemia (AML), reduction of SLC29A1 expression decreased the cytotoxic effects of AraC in AML cell lines. Also, a polymorphism (rs3734703) in SLC29A1 was significantly associated with complete remission (CR) in AML patients [2]. In chronic hepatitis C patients receiving telaprevir-based triple therapy, the SLC29A1 rs760370 GG genotype was associated with the severity of ribavirin-induced anemia [3]. In pancreatic cancer, ZIP4 overexpression inhibited the expression of the gemcitabine transporter ENT1 (encoded by SLC29A1), reducing gemcitabine uptake by pancreatic cancer cells and increasing resistance to chemotherapy [5]. In brown adipose tissue, ENT1-deficiency increased extracellular inosine levels, enhancing thermogenic adipocyte differentiation, BAT activity, and counteracting diet-induced obesity [4].

In conclusion, Slc29a1 is essential for nicotinamide transport and metabolism, and its function is closely related to various disease conditions. The findings from in vitro cell-based experiments and in vivo studies in patients highlight its importance in cancer chemotherapy response, anemia in hepatitis C treatment, and energy metabolism-related diseases. Understanding Slc29a1 can provide new insights into disease mechanisms and potential therapeutic targets.