Slc1a6, also known as EAAT4, is a member of the solute carrier family 1 and functions as a high-affinity glutamate transporter. It mediates the cellular uptake of glutamate by co-transporting three sodium ions and one proton, while counter-transporting one potassium ion. This process is crucial for terminating excitatory neurotransmission and protecting the central nervous system (CNS) from glutamate-induced neurotoxicity [2,5,7]. Glutamate transporters, including Slc1a6, are involved in the glutamatergic system, which has been implicated in many biological processes and diseases [4].

In nasopharyngeal carcinoma (NPC), radioresistant NPC cell lines (HONE1-IR and CNE2-IR) showed up-regulation of Slc1a6. Down-regulation of Slc1a6 enhanced cisplatin sensitivity in these cell lines. The expression of Slc1a6 was induced during radiation treatment and correlated with poor prognosis of NPC patients. Up-regulation of Slc1a6 led to an elevation of glutamate levels and drug-resistant gene expression, resulting in reduced cisplatin sensitivity [1]. In schizophrenia, individuals carrying at least one C allele of rs35753505 (near the NRG1 gene) showed decreased expression of Slc1a6 in the molecular layer of the cerebellar hemispheres. Also, association studies in the Japanese population found significant associations of schizophrenia with a genotype and haplotypes in the Slc1a6 region, suggesting that a susceptibility locus for schizophrenia may be located within or nearby Slc1a6 [3,6].

In conclusion, Slc1a6 is an important glutamate transporter with a key role in regulating glutamate levels in the CNS. Studies on Slc1a6 have provided insights into its functions in diseases such as nasopharyngeal carcinoma and schizophrenia. Understanding the role of Slc1a6 in these disease conditions could potentially lead to the development of new therapeutic strategies for treatment.