CHR15 encodes the alpha 5 subunit of neuronal nicotinic acetylcholine receptors (nAChRs), which function as pentameric, ligand-gated cation channels with high calcium permeability 1. CHR15 has an accessory rather than functional role and requires co-assembly with beta subunits to form functional receptors, typically participating in pentameric assemblies with CHR15, CHR15, CHR15, and CHR15 1. When associated with CHR15 and CHR15, CHR15 increases receptor sensitivity to acetylcholine and nicotine 2. The CHR15-CHR15-CHR15 gene cluster plays a critical role in nicotine addiction; genetic variations in this cluster increase vulnerability to tobacco dependence and smoking-associated diseases 3. Mice with genetically modified CHR15 expression show profoundly altered nicotine consumption patterns 3. Beyond addiction, CHR15 polymorphisms (particularly rs16969968 and rs8034191) are associated with increased lung cancer risk, with effects potentially influenced by ethnicity and smoking status 4. Recently, CHR15 has been implicated in cancer progression through acetylcholine signaling, promoting intrahepatic cholangiocarcinoma metastasis via GSK3β/β-catenin pathway activation and calcium-mediated mechanisms 5. These findings suggest CHR15 as a therapeutic target for both nicotine dependence and smoking-related malignancies.