The glycine receptor (abbreviated as GlyR or GLR) is the receptor of the amino acid neurotransmitter glycine. GlyR is an ionotropic receptor that produces its effects through chloride current. It is one of the most widely distributed inhibitory receptors in the central nervous system and has important roles in a variety of physiological processes, especially in mediating inhibitory neurotransmission in the spinal cord and brainstem. The receptor can be activated by a range of simple amino acids including glycine, β-alanine and taurine, and can be selectively blocked by the high-affinity competitive antagonist strychnine. Caffeine is a competitive antagonist of GlyR. Cannabinoids enhance the function. Gephyrin has been shown to be necessary for GlyR clustering at inhibitory synapses. GlyR is known to colocalize with the GABAA receptor on some hippocampal neurons. Nevertheless, some exceptions can occur in the central nervous system where the GlyR α1 subunit and gephyrin, its anchoring protein, are not found in dorsal root ganglion neurons despite the presence of GABAA receptors. History Glycine and its receptor were first suggested to play a role in inhibition of cells in 1965. Two years later, experiments showed that glycine had a hyperpolarizing effect on spinal motor neurons due to increased chloride conductance through the receptor. Then, in 1971, glycine was found to be localized in the spinal cord using autoradiography. All of these discoveries resulted in the conclusion that glycine is a primary inhibitory neurotransmitter of the spinal cord that works via its receptor. Arrangement of subunits Strychnine-sensitive GlyRs are members of a family of ligand-gated ion channels. Receptors of this family are arranged as five subunits surrounding a central pore, with each subunit composed of four α helical transmembrane segments. There are presently four known isoforms of the ligand-binding α-subunit (α1-4) of GlyR (GLRA1, GLRA2, GLRA3, GLRA4) and a single β-subunit (GLRB). The adult form of the GlyR is the heteromeric α1β receptor, which is believed to have a stoichiometry (proportion) of three α1 subunits and two β subunits or four α1 subunits and one β subunit. The embryo form on the other hand, is made up of five α2 subunits. The α-subunits are also able to form functional homopentamers in heterologous expression systems in African clawed frog oocytes or mammalian cell lines, which are useful for studies of channel pharmacokinetics and pharmacodynamics. The β subunit is unable to form functional channels without α subunits but determines the synaptic