SLC6A5

SLC6A5 is a human gene that encodes glycine transporter 2 (GlyT2), a member of the solute carrier family 6 (SLC6). GlyT2 is a sodium- and chloride-dependent transporter that reuptakes glycine from the synaptic cleft into presynaptic terminals, thereby helping terminate glycinergic neurotransmission.

Structurally, GlyT2 is a multi-pass membrane protein with characteristics typical of SLC6 transporters, including twelve transmembrane domains. It functions to maintain glycine availability for release and to regulate the strength and duration of inhibitory glycinergic signaling.

Expression of SLC6A5 is greatest in glycinergic interneurons of the spinal cord and brainstem, where GlyT2 supplies glycine for release and prevents depletion during repetitive stimulation. The transporter supports inhibitory glycinergic tone in the dorsal horn and other glycinergic pathways.

Genetic mutations in SLC6A5 have been associated with hyperekplexia, a rare neurological disorder characterized by exaggerated startle responses and muscle stiffness. Many cases are inherited in an autosomal recessive pattern, though inheritance can vary with different mutations.

From a research and therapeutic perspective, GlyT2 is a target for analgesic development: inhibitors of GlyT2 can elevate extracellular glycine and enhance inhibitory glycinergic transmission, potentially providing relief for chronic pain. Ongoing work also investigates the role of SLC6A5 variants in neurodevelopmental and motor disorders, and the transporter’s pharmacology in animal models.