SLC13A3 functions as a high-affinity sodium-dependent dicarboxylate cotransporter that transports metabolites across cellular membranes with a 3:1 Na+:anion stoichiometry 1. The transporter accepts substrates including citric acid cycle intermediates such as succinate and alpha-ketoglutarate, as well as citrate and glutathione 23. Recent studies have identified SLC13A3 as a key itaconate transporter, importing this immunoregulatory metabolite from macrophages into various cell types 45. In hepatocytes, itaconate uptake via SLC13A3 activates TFEB-dependent lysosomal biogenesis, enhancing antibacterial innate immunity 4. However, in cancer contexts, SLC13A3-mediated itaconate transport promotes immune evasion by activating the NRF2-SLC7A11 pathway, conferring resistance to ferroptosis and immunotherapy 56. In liver cancer, SLC13A3 acts downstream of Ξ²-catenin signaling and regulates glutathione transport, supporting tumor cell survival through mTOR signaling and autophagy resistance 3. SLC13A3 mutations are associated with acute reversible leukoencephalopathy with increased urinary alpha-ketoglutarate. The transporter represents a promising therapeutic target for metabolic disorders and cancer, with small molecule inhibitors showing efficacy in preclinical models 37.
No tissue expression data available for this gene.