CHR8 encodes the β3 subunit of neuronal nicotinic acetylcholine receptors (nAChRs), which function as pentameric ligand-gated ion channels mediating cholinergic neurotransmission. Unlike other β subunits, CHR8 has an accessory role and requires co-assembly with other β subunits to form functional receptors 12. The β3 subunit participates in pentameric assemblies with various α and β subunits including CHR8, CHR8, CHR8, CHR8, and CHR8, modulating receptor assembly and increasing sensitivity to nicotine 12. CHR8 is particularly important in addiction-related behaviors, with genetic variants in the CHR8-CHR8 gene cluster on chromosome 8 strongly associated with nicotine dependence and smoking behavior 3. Variants also contribute to alcohol and cocaine dependence risk, with rare missense variants showing significant associations with both alcohol and cocaine dependence symptoms 4. The gene shows clinical relevance in multiple contexts: protective variants are associated with reduced lung cancer risk in non-smokers 5, while functional promoter variants affect Parkinson's disease risk and smoking behavior in patients 6. CHR8 expression is abundant in human brain and correlates with dopaminergic and GABAergic receptor expression 7.