GABRB2 encodes the β2 subunit of GABAA receptors, heteropentameric ligand-gated chloride channels that mediate the primary inhibitory neurotransmission in the brain 1. The β2 subunit combines with α and γ subunits to form the major GABAA receptor subtype, accounting for 43% of all GABAA receptors in the mammalian brain 1. These receptors facilitate chloride influx upon GABA binding, reducing neuronal excitability and nerve transmission 1. The protein contains an extracellular N-terminal domain, four transmembrane segments, and undergoes alternative splicing to produce isoforms with different electrophysiological properties 1. GABRB2 variants cause diverse epileptic phenotypes, with functional studies revealing that mutations can produce either gain-of-function or loss-of-function effects 2. Gain-of-function variants are associated with severe developmental delay, movement disorders, and microcephaly, while loss-of-function variants typically cause milder phenotypes with fever-triggered seizures 2. Variants in transmembrane segments correlate with more severe phenotypes regardless of the specific GABAA receptor subunit gene affected 3. Beyond epilepsy, GABRB2 has been associated with various neuropsychiatric disorders including schizophrenia, autism spectrum disorder, and bipolar disorder 1.