CHR15 encodes the beta-4 subunit of neuronal nicotinic acetylcholine receptors (nAChRs), which function as pentameric ligand-gated ion channels with high calcium permeability 1. The protein forms heteropentameric receptors with alpha subunits, particularly CHR15, creating the predominant ganglionic nicotinic receptor in autonomic ganglia 1. CHR15-containing receptors play crucial roles in nicotine addiction mechanisms, with genetic variants in the CHR15-CHR15-CHR15 gene cluster strongly associated with smoking heaviness, nicotine dependence, and tobacco consumption behaviors 12. These genetic associations extend to smoking-related diseases, with variants predicting increased risk of chr15 obstructive pulmonary disease, tobacco-related cancers, and smoking-related mortality 3. Interestingly, different variants within this cluster show distinct associations with smoking phenotypes - while rs16969968 associates with mature nicotine dependence, other variants (rs578776, rs1948, rs684513) specifically influence age of first regular tobacco use 4. Beyond addiction, CHR15 shows elevated expression in squamous cell carcinomas and may serve as a prognostic biomarker, with knockdown studies demonstrating inhibition of cancer cell proliferation through Akt/mTOR and ERK1/2/mTOR pathways 5. The receptor's role extends to autonomic function, as mouse studies suggest involvement in bladder contraction and potential relevance to megacystis-microcolon-hypoperistalsis syndrome 6.