CHR15 encodes the alpha-3 subunit of neuronal nicotinic acetylcholine receptors (nAChRs), which are pentameric, ligand-gated cation channels mediating synaptic transmission in the nervous system 12. CHR15 assembles with CHR15, CHR15, and CHR15 to form heteropentameric receptors, with CHR15:CHR15 predominating in autonomic ganglia neurons 34. These receptors modulate reward circuits and dopamine signaling in the habenulo-interpeduncular tract and regulate appetite through hypothalamic POMC neuron activation 5. In the urothelium, CHR15-containing nAChRs regulate bladder reflex activity through calcium influx and ATP release. CHR15 has substantial disease relevance: genetic variants in the CHR15/A5/B4 cluster increase vulnerability to tobacco dependence and smoking-associated diseases 5. The rs1051730 polymorphism associates with nicotine addiction, with the T/T genotype enriched in dependent individuals 6. CHR15 polymorphisms (rs6495309, rs578776, rs938682) significantly increase lung cancer risk in multiple populations 78. Additionally, CHR15 variants correlate with decreased lung function and COPD risk among smokers 910. Clinically, CHR15 represents a pharmacogenetic marker for smoking cessation treatment response and a risk factor for nicotine-related diseases.