GABRA5 encodes the alpha-5 subunit of GABA-A receptors, heteropentameric ligand-gated chloride channels that mediate inhibitory neurotransmission in the brain 1. The gene is located on chromosome 15-q13 within an imprinted region and spans 86 kb organized into 11 exons 2. GABRA5-containing receptors are primarily extrasynaptic and contribute to tonic GABAergic inhibition, particularly in the hippocampus where they influence learning and memory processes. The gene exhibits complex transcriptional regulation through three alternative first exons (1A, 1B, 1C) that generate distinct mRNA isoforms with tissue- and region-specific expression patterns in the brain 3. Pathogenic variants in GABRA5 cause early-onset epilepsy and developmental delay through altered receptor function - a de novo missense variant (p.V294L) produces receptors with 10-fold increased GABA sensitivity but reduced maximal current due to enhanced desensitization 1. GABRA5 is associated with multiple neurological conditions including developmental and epileptic encephalopathy, panic disorder, and potentially depression 456. Mouse studies suggest GABRA5 deficiency reduces anxiety-related behaviors and stress responses, indicating its role in HPA axis regulation 7.