GABRR2 encodes the rho-2 subunit of GABA-A receptors, pentameric ligand-gated chloride channels that mediate inhibitory neurotransmission through GABA, the brain's primary inhibitory neurotransmitter 1. The protein forms homomeric rho-containing GABA-A receptors where GABA binding at rho intersubunit interfaces triggers selective chloride ion influx across the neuronal membrane 2. GABRR2 is located on chromosome 6-q21, tightly linked with GABRR1 1, and functions in cerebellar Purkinje neurons mediating both tonic (extrasynaptic) and phasic (synaptic) transmission, with roles in retinal neurotransmission 3. Disease relevance of GABRR2 variants is substantial. Polymorphisms in GABRR2, including the coding variant Met430Thr (rs282129), show significant association with alcohol dependence, particularly early-onset forms 2. GABRR2 variants also associate with serum creatinine levels, suggesting roles in glomerular function 4. Additionally, GABRR2 polymorphisms interact with perceived parental support in modulating adolescent depressive symptoms 5, and genetic variants influence general cognitive ability in healthy populations 6. Notably, GABA receptor genes including GABRR2 show associations with autism susceptibility through complex gene-gene interactions 7. Clinically, GABRR2 represents a candidate therapeutic target for alcohol dependence and mood-related disorders, though variants showed limited association with antiepileptic drug resistance in one population 8.