CNT2

CNT2 (SLC28A2) is a sodium-dependent concentrative nucleoside transporter that mediates active cellular uptake of nucleosides and contributes to maintenance of nucleotide salvage pathways[1][2]. Mechanistically, CNT2 functions as a unidirectional Na+-coupled transporter and displays preferential transport of purine nucleosides, thereby supporting intracellular nucleoside availability for metabolic and signaling processes[2][3]. This transport activity is biologically important because nucleoside salvage complements de novo nucleotide biosynthesis and helps sustain cellular nucleotide pools required for normal cellular function[4]. CNT2 is expressed beyond classical epithelial barriers and participates in transcellular nucleoside flux, linking membrane transport to broader regulation of extracellular and intracellular nucleoside homeostasis[2]. In disease- and drug-related contexts, nucleoside transporters influence the disposition, efficacy, and cellular uptake of nucleoside-derived antiviral and anticancer agents, making CNT2 relevant to pharmacological research and experimental drug-response models[5][3]. Compared with related SLC28 family members, CNT2 is distinguished by its preference for purine nucleosides, whereas CNT1 primarily transports pyrimidine nucleosides and CNT3 exhibits broader substrate selectivity for both purines and pyrimidines with distinct ion-coupling properties[2][3]. Therefore, isoform-specific substrate recognition provides an important framework for mechanistic studies of nucleoside transport and for the evaluation of transporter-mediated drug uptake in experimental systems[5][3].