Gamma-aminobutyric acid type B receptor subunit 2

GABBR2 encodes the gamma-aminobutyric acid type B receptor subunit 2, a component of the heterodimeric GABA-B receptor (UniProt: O75899). Within this receptor complex, GABBR2 mediates coupling to G proteins and modulates downstream signaling cascades including adenylate cyclase, phospholipase A2, potassium channels, and calcium channels. The receptor plays a critical role in fine-tuning inhibitory synaptic transmission at both pre- and postsynaptic sites and has been implicated in hippocampal long-term potentiation and sleep regulation (UniProt: O75899).

GABBR2 mutations have been associated with neurodevelopmental conditions including developmental and epileptic encephalopathy 59 (DEE59) and neurodevelopmental disorder with poor language and loss of hand skills (NDPLHS), both characterized by early-onset seizures and cognitive impairment (UniProt: O75899).

In Alzheimer's disease, GABBR2 is downregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.364 across the examined subcellular fractions (Chaparral AD proteomics). This reduction may contribute to altered GABAergic inhibitory signaling in the AD brain.