Sodium- and chloride-dependent GABA transporter 2 (GAT-2) (GAT-2)

Sodium- and chloride-dependent GABA transporter 2 (GAT-2), encoded by the SLC6A13 gene, is a transmembrane protein responsible for the reuptake of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and the osmolyte betaine (UniProt: P48066). Unlike GAT-1, which is predominantly found in neurons, GAT-2 is highly expressed in peripheral tissues such as the liver and kidneys, as well as in the blood-brain barrier, specifically within the arachnoid membrane and ependymal cells (PubMed: 15504334). Its primary function is to regulate extracellular GABA concentrations, thereby modulating inhibitory signaling in the central nervous system and maintaining osmotic balance in peripheral tissues. In clinical contexts, GAT-2 is associated with epilepsy, as its dysfunction can lead to altered seizure thresholds, and it has been investigated for its role in liver fibrosis and metabolic regulation (PubMed: 25636461). While most current GABAergic drugs like tiagabine primarily target GAT-1, GAT-2 is a subject of research for the development of selective inhibitors to treat refractory epilepsy and other neurological conditions. Experimental compounds such as NNC-05-2090 have been used to study its specific pharmacological profile and therapeutic potential (PubMed: 12606503).

Other names

SLC6A13Solute carrier family 6 member 13GAT2GABA transporter 2

Inhibition of GABA reuptake from the extracellular space into cells, thereby increasing GABAergic tone.