Glycine transporter 2 (GlyT2)

Glycine transporter 2 (GlyT2, SLC6A5) is a sodium- and chloride-dependent membrane transporter localized predominantly to the presynaptic terminals of glycinergic neurons in the spinal cord and brainstem[2]. It belongs to the solute carrier 6 (SLC6) family of neurotransmitter transporters and specifically mediates the high-affinity uptake of glycine from the synaptic cleft back into presynaptic terminals, playing a critical role in maintaining synaptic vesicle glycine levels for inhibitory neurotransmission[1][2][5]. GlyT2's substrate specificity is primarily limited to glycine, with certain mutations broadening its selectivity[1][3]. Loss-of-function mutations cause hyperekplexia, a rare neurological disorder marked by exaggerated startle response and stiffness due to impaired glycinergic signaling[5]. GlyT2 is a validated therapeutic target for modulating glycinergic neurotransmission, and selective inhibitors (e.g., ALX1393, ORG25543) are being investigated for the treatment of neuropathic pain and other neurological diseases[6][7].

Other names

SLC6A5GlyT-2Sodium- and chloride-dependent glycine transporter 2solute carrier family 6 member 5

Competitive or noncompetitive inhibition (depending on compound and concentration) of glycine reuptake, leading to increased extracellular glycine and enhanced inhibitory synaptic transmission[6][7]