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. GlyR is a member of the pentameric Cys-loop ion channel receptor family. Functional Cys-loop receptors comprise homomeric or heteromeric pentameric oligomers with each of the five subunits arranged symmetrically in a ring around a central ion-conducting pore. Several developmentally and regionally regulated GlyR isoforms exist, which result from a differential expression of the GlyR α (α1- α4) and β subunit genes. Each GlyR subunit comprises a large extracellular amino-terminal domain that harbors the ligand-binding sites and the eponymous Cys-loop. This connects to a bundle of four α-helical transmembrane domains (labelled M1–M4) with a large intracellular domain between M3 and M4 and a short extracellular C-terminal tail². The human α4 subunit is considered a pseudogene on the grounds that it incorporates a premature stop codon upstream of the final TM4 domain³.

The α4 subunit has been found in the adult mouse retina where it clusters together with synaptic markers such as bassoon or gephyrin. Furthermore, GlyR α4 transcripts have been detected in the white matter tract of the developing spinal cord from mice. The avian α4 mRNA was also found in dorsal root ganglia and genital ridge ⁴.

Although the function of GlyR α4 at its sites of expression is still unknown, homomeric α4 receptors are able to form fully functional glycine-gated Cl⁻ channels in vitro that can be antagonized with strychnine⁵.