Solute carrier family 13 member 5 (SLC13A5)

Solute carrier family 13 member 5 (SLC13A5), also known as the sodium-coupled citrate transporter (NaCT), is a plasma membrane protein that mediates the uptake of extracellular citrate into the cytosol of cells, particularly in the liver and brain. In the liver, SLC13A5 plays a critical role in metabolic homeostasis by providing citrate as a precursor for de novo lipogenesis and cholesterol synthesis. Consequently, the transporter is a key therapeutic target for metabolic diseases; its inhibition has been shown to protect against diet-induced obesity, insulin resistance, and non-alcoholic fatty liver disease (NAFLD) in preclinical models. In the brain, SLC13A5 is essential for maintaining appropriate intracellular citrate levels for energy production and the synthesis of neurotransmitters such as GABA and glutamate. Clinically, the importance of SLC13A5 is highlighted by the fact that biallelic loss-of-function mutations in humans result in a severe, rare neurodevelopmental disorder known as SLC13A5-related epilepsy or early infantile epileptic encephalopathy 25 (EIEE25). This condition is characterized by neonatal-onset seizures and significant global developmental delays. While pharmacological inhibitors like PF-06760805 are being investigated for metabolic indications, they must be designed to avoid central nervous system entry to prevent potential neurological side effects. Conversely, gene therapy approaches like TSHA-105 are under development to restore functional SLC13A5 in patients suffering from transporter deficiency.

Other names

Sodium-coupled citrate transporterNaCTmIndyINDY homologSodium-dependent citrate transporterEarly infantile epileptic encephalopathy 25EIEE25Solute carrier family 13 member 5 (sodium-dependent citrate transporter)