Solute carrier family 13 member 5 (SLC13A5) (SLC13A5)

Solute carrier family 13 member 5 (SLC13A5), often identified by its activity as hepatoma cell membrane citrate-binding sites, is a sodium-coupled transporter primarily expressed in the liver (PubMed: 26431204). It facilitates the entry of extracellular citrate into the cytoplasm, where it is converted into acetyl-CoA to support de novo lipogenesis and cholesterol synthesis (PubMed: 28807918). In hepatoma cells, SLC13A5 is frequently upregulated to meet the high metabolic demands of rapidly dividing cancer cells, making it a key driver of tumor growth (PubMed: 30143544). Targeting these binding sites with small molecule inhibitors like PF-06760805 aims to disrupt the supply of carbon sources for lipid production, thereby inhibiting oncogenic progression and addressing metabolic disorders like non-alcoholic fatty liver disease (PubMed: 30651350). While a promising therapeutic avenue, drug design must account for the transporter's role in the brain, as genetic deficiency is linked to Kohlschütter-Tönz syndrome, a severe form of epilepsy (PubMed: 24859130). The transporter's high specificity for citrate and its localized expression in the liver make it an attractive target for precision metabolic therapy. Current research is focused on developing liver-targeted inhibitors to minimize systemic toxicity and neurological risks.

Other names

Plasma membrane citrate transporterPMCTSodium-coupled citrate transporterNaCTHepatoma cell membrane citrate-binding sitesINDY homolog

Inhibition of the SLC13A5 transporter to prevent extracellular citrate uptake, thereby reducing the availability of cytosolic acetyl-CoA for lipid and cholesterol synthesis.