GABAB2

GABA-B receptor subunit 2, encoded by the GABBR2 gene in humans, is one of the two essential components of the GABA-B receptor. It forms a functional receptor together with GABBR1, with GABBR1 providing the ligand-binding capacity and GABBR2 contributing to proper receptor trafficking and signaling.

GABA-B receptors are metabotropic G-protein-coupled receptors in the class C family. The heterodimeric receptor couples to Gi/o proteins, leading to inhibition of adenylyl cyclase, activation of G protein–gated inwardly rectifying potassium channels (GIRKs), and inhibition of voltage-gated calcium channels. These actions reduce neuronal excitability and neurotransmitter release, producing inhibitory effects in the nervous system.

Expression of GABBR2 is widespread in the central nervous system, with substantial presence in regions such as the cortex, hippocampus, and thalamus. The receptor is found at both presynaptic and postsynaptic sites, contributing to the regulation of synaptic transmission and network activity.

Clinical and research relevance: pharmacologically, baclofen, a GABA-B receptor agonist, is used clinically to treat spasticity, illustrating the receptor’s therapeutic potential. Dysregulation of GABA-B signaling has been studied in relation to epilepsy, anxiety disorders, addiction, and chronic pain. Genetic variation and functional changes in GABBR2 have been explored in relation to various neuropsychiatric conditions, though findings continue to evolve.

Research models show that disruption of GABBR2 impairs receptor assembly, trafficking, and signaling, underscoring the subunit’s essential role in the proper function of GABA-B receptors. As a drug target, GABBR2-containing receptors remain a focus for strategies to modulate inhibitory neurotransmission in the CNS.