GABRA6 encodes the alpha-6 subunit of GABA-A receptors, which are ligand-gated chloride channels central to GABAergic inhibitory neurotransmission. When activated by GABA, these pentameric receptors allow chloride influx that hyperpolarizes neurons and reduces action potential generation. Alpha-6 subunits localize to both synaptic and extrasynaptic sites, where they contribute to tonic inhibition and regulate glutamatergic signaling. GABRA6 variants influence hypothalamic-pituitary-adrenal axis function and stress physiology; the T1521C polymorphism associates with greater cortisol and blood pressure responses to psychological stress and enhanced anxiety under environmental adversity 12. The rs3219151 T allele increases suicide risk specifically in carriers exposed to recent negative life events, with effects on depression, anxiety, and specific suicidal ideation markers 2. TT carriers show accelerated telomere shortening in CD8+CD28+ leukocytes, suggesting cellular aging 3. Multiple GABRA6 variants and polymorphisms confer epilepsy susceptibility across diverse populations, including in idiopathic generalized epilepsy and drug-resistant epilepsy 456. Rare missense variants associate with bipolar disorder risk 7. Benzodiazepines, barbiturates, brexanolone, and other GABAergic modulators targeting GABA-A receptors are approved for seizure, anxiety, and sleep disorders.