GABRG2 encodes the gamma-2 subunit of GABAA receptors, heteropentameric ligand-gated chloride channels that mediate inhibitory neurotransmission in the brain 1. The gamma-2 subunit is essential for receptor trafficking and synaptic localization, playing a critical role in both synaptic and extrasynaptic GABAergic signaling 1. When activated by GABA, these receptors allow chloride influx, hyperpolarizing neurons and reducing their excitability 1. GABRG2 variants are strongly associated with epilepsy syndromes, particularly genetic epilepsy with febrile seizures plus (GEFS+), developmental and epileptic encephalopathy, and generalized epilepsy 23. The C588T polymorphism increases genetic generalized epilepsy risk, particularly in Asian populations 4. Functional studies reveal that GABRG2 mutations can cause both gain-of-function and loss-of-function effects, with transmembrane domain variants typically associated with more severe phenotypes 15. Neuroimaging studies in GABRG2 variant carriers show altered functional connectivity in somatosensory cortex and striatothalamic networks 6. The protein interacts with approved antiepileptic drugs, suggesting potential therapeutic targeting opportunities 4.