Gephyrin is a highly conserved, intracellular scaffolding protein responsible for the post-synaptic anchoring and assembly of the inhibitory glycine and γ-aminobutyric acid type A receptors (GlyR and GABA_AR); it essentially anchors the receptors, by auto-oligomerization, to the cytoskeleton^1,2.

GABAergic transmission is important for the mediation of neuronal excitability and has a crucial role in neurodevelopment, throughout the central and peripheral nervous systems (especially via GABA_AR). Glycinergic neurons on the other hand control motor functions and sensory signaling as well as take part in pain transmission in the spine's dorsal horn. Importantly, gephyrin has a 1:1 stoichiometry with GlyR^3,4.

Up-to-date atomic force microscopy data of gephyrin has shown that it forms trimers with multiple conformations. It is a modular construct with three domains: an N-terminal G-, a central C- and a C-terminal E-domain. Recent work suggests also that gephyrin regulates neuronal differentiation by anchoring small cytoskeletal-related signaling molecules at unique subcellular locations^2,5,6.