Apart from its obvious biochemical functions, glycine is also an important inhibitory neurotransmitter. Following depolarization, glycine is released from synaptic vesicles, binds to glycine receptors (GlyRs) on postsynaptic membranes thereby causing hyperpolarization of postsynaptic neurons due to the massive influx of Cl^- ions. Glycine is then taken up from the synaptic cleft via the glycine transporters GlyT1 and GlyT2¹.

GlyT1 and GlyT2 belong to the SLC6, Na⁺/Cl^- dependent transporter family, of which members include transporters for GABA, serotonin, dopamine and norepinephrine². Like all SLC6 members, GlyT1 and GlyT2 have 12 transmembrane domains and intracellular N- and C-terminals. Both can be found in different splice variants^3,4. SLC6 transporters undergo post-translational modifications. For instance, GlyT1 and GlyT2 are glycosylated, which is important for their membrane trafficking⁵.

Phosphorylation of these two transporters also takes place in a PKC-dependent manner, which may lead to down regulation of both transporters⁶. Pharmacologically, GlyT1 and GlyT2 can be differentiated by applying sarcosine which inhibits GlyT1 but not GlyT2⁷.

GlyT1 and GlyT2 are broadly expressed in the nervous system; GlyT1 is concentrated in glial cells, while GlyT2 is present in glycenergic neurons in the spinal cord, brainstem and cerebellum¹. GlyT1 can also be detected in the pancreas, uterus, stomach, spleen, liver and retina⁴.

GlyT1 has become a target for the treatment of schizophrenia, although a defect of the protein is not directly associated with the disorder. Inhibiting GlyT1 should lead to the increase in glutamatergic pathways, thereby decreasing psychotic effects in schizophrenic individuals. GlyT2 has been associated with hyperekplexia, a motor disorder characterized by neonatal hypertonia and startle reflex⁸.