Equilibrative nucleoside transporter 3 (ENT3)

Equilibrative nucleoside transporter 3 (ENT3), encoded by the SLC29A3 gene, is a member of the solute carrier (SLC) family 29 of nucleoside transporters. Unlike other ENT family members, ENT3 is primarily localized to intracellular membranes, especially the lysosomes and mitochondria, rather than the plasma membrane. It mediates pH-dependent transport of nucleosides out of the lysosome (for salvage and reuse) and into mitochondria (for mitochondrial DNA/RNA synthesis and repair), thus being critical in nucleoside homeostasis and cell metabolism. Loss-of-function mutations in SLC29A3 disrupt nucleoside transport, leading to multisystem genetic diseases characterized by histiocytosis, skin hyperpigmentation, endocrine dysfunction, and inflammatory syndromes. ENT3 also mediates cellular uptake of certain nucleoside analog drugs, which may possess mitochondrial toxicity potential. Recent studies have revealed that ENT3 dysfunction can abnormally activate immune and inflammatory signaling through toll-like receptors and MAPK pathways, providing insight for emerging therapeutic interventions.

Other names

SLC29A3solute carrier family 29 member 3hENT3FLJ11160HCLAPHJCDPHIDequilibrative nucleoside transporter 3solute carrier family 29 (equilibrative nucleoside transporter) member 3solute carrier family 29 (nucleoside transporters) member 3

Facilitation of transport of endogenous nucleosides and nucleoside analog drugs across lysosomal and mitochondrial membranes (salvage pathway), intracellular nucleoside redistribution, potential role in drug-induced mitochondrial toxicity