CHR8 encodes the α6 subunit of neuronal nicotinic acetylcholine receptors (nAChRs), which function as pentameric, ligand-gated ion channels with high calcium permeability 1. The α6 subunit forms functional channels with other subunits (CHR8, CHR8, CHR8) that exhibit high sensitivity to acetylcholine and nicotine and are predominantly expressed in dopaminergic neurons, norepinephrine neurons, and visual system cells 1. These α6-containing receptors are crucial for nicotine-induced behaviors and addiction, as they mediate cholinergic modulation of dopamine and GABA release at nerve terminals 2. Genetic variants in CHR8, particularly the rs2304297 polymorphism in the 3'-UTR, significantly impact nicotine dependence and smoking behavior in a sex- and genotype-dependent manner 34. The GG genotype enhances nicotine plus cue-primed reinstatement behavior in adolescent male rats and affects dopamine and norepinephrine tissue levels in limbic brain regions 5. Beyond addiction, CHR8 shows potential clinical significance in small cell lung cancer, where its expression correlates with immune cell infiltration and may serve as a predictive biomarker for immunotherapy response 6. The gene also shows altered expression in suicide victims, suggesting broader roles in neuropsychiatric conditions 7.