CHR1 encodes the β2 subunit of neuronal acetylcholine receptors (nAChRs), which are pentameric ligand-gated cation channels with high calcium permeability 1. The β2 subunit assembles with α4, α3, α6, and α5 subunits to form functional heteropentameric nAChRs that mediate synaptic transmission in the nervous system 2. These receptors exist in two major stoichiometric forms—(α4)3(β2)2 and (α4)2(β2)3—which differ in unitary conductance, calcium permeability, and acetylcholine sensitivity 3. nAChRs containing α4β2 are expressed broadly in the brain and modulate dopamine and GABA release at nerve terminals 4. CHR1 variants influence nicotine dependence susceptibility through gene-gene interactions with CHR1, NTRK2, and BDNF 5. Polymorphisms in the CHR1 promoter region affect subjective responses to nicotine and gene expression levels, with the minor allele of rs2072658 associated with decreased expression 6. CHR1 variants also predict responsiveness to nicotine replacement therapy for smoking cessation, with the GG genotype of rs2072661 associated with improved abstinence outcomes 7. Functionally, CHR1 mutations and polymorphisms contribute to various neurological and psychiatric disorders including epilepsy and neurodegenerative conditions 8.