Slc13a5, also known as NaCT or mINDY, is a Na⁺ -coupled citrate co-transporter. It mediates the entry of extracellular citrate into the cytosol, playing a crucial role in maintaining cellular metabolic homeostasis. The citrate it transports is involved in diverse biochemical pathways such as fatty acid and cholesterol synthesis, fatty acid oxidation, glycolysis, and gluconeogenesis in the liver, and neurotransmitter synthesis in neurons [2,4].

In mouse models, deletion of Slc13a5 leads to a beneficial phenotype, protecting against diet-induced obesity and diabetes [4]. However, in humans, loss-of-function mutations in SLC13A5 cause severe epileptic encephalopathy, with patients experiencing seizure onset within the first week of life, along with developmental delay and intellectual disability [1,3,4]. These differences may be due to species-specific differences in the transporter's functional features; human SLC13A5 is a high-capacity transporter while mouse Slc13a5 is a low-capacity one [4].

In conclusion, Slc13a5 is essential for normal metabolic and neuronal function. Mouse models of Slc13a5 knockout have been valuable in revealing its role in metabolism, while human genetic studies have highlighted its critical role in preventing epileptic encephalopathy. Understanding the function of Slc13a5 through these models may offer potential therapeutic strategies for related metabolic and neurological disorders [1,4].