The amino acid glycine mediates neuronal inhibition by activating glycine receptors (GlyRs), which are ligand-gated chloride channels of the nicotinic acetylcholine receptor superfamily. GlyRs are known to mediate postsynaptic inhibition in spinal cord, brain stem and some higher brain regions¹. GlyRs are members of the pentameric Cys-loop family of ionotropic neurotransmitter receptors.

GlyRs are composed of homologous α (α1-α4) and β subunits. Upon synthesis at the endoplasmic reticulum (ER), all GlyRα subunits can assemble into functional homopentamers that are inserted into the plasma membrane. In contrast, the GlyRβ subunit requires stoichiometric coassembly with GlyRα subunits for ER exit and cell surface expression. Each subunit consists of an extended N-terminal extracellular domain, four transmembrane domains, and a large intracellular loop between transmembrane domains 3 and 4. The β subunit is responsible for synaptic localization of the GlyRs by interacting with the postsynaptic scaffolding protein gephyrin. GlyRβ subunit is reported to interact with the proteins Vacuolar Protein Sorting 35 (Vps35) and Neurobeachin (Nbea)².

GlyRβ mRNA is abundantly found throughout the late embryonic and postnatal brain³.

Mutations in GLRB, the gene encoding GlyRβ, have been discovered in patients with hyperekplexia⁴, in the mouse mutant spastic⁵ and the zebrafish bandoneon mutant⁶.