CHR15 encodes the α5 subunit of neuronal nicotinic acetylcholine receptors (nAChRs), which function as pentameric, ligand-gated cation channels with high calcium permeability. The α5 subunit plays an accessory role and only forms functional receptors when co-assembled with beta subunits, participating in pentameric assemblies that include α3, α4, and β2/β4 subunits. When associated with α4 and β2 subunits, CHR15 increases receptor sensitivity to acetylcholine and nicotine, thereby modulating synaptic transmission in the nervous system and neuromuscular junction. Genetic variation in CHR15, particularly the rs16969968 polymorphism, has been robustly associated with increased vulnerability to tobacco dependence and smoking-associated diseases 1. This polymorphism causes an amino acid change at position 398 of the α5 protein and influences daily cigarette consumption equivalently to approximately 1 cigarette per day 2. In humans, the variant is associated with altered dopaminergic neuron responses during chr15 nicotine exposure and withdrawal 3. Beyond nicotine addiction, CHR15 contributes to cancer progression. Nicotine-induced CHR15 activation promotes proliferation and metastasis in head and neck squamous cell carcinoma through the MEK/ERK pathway 4, while acetylcholine/CHR15 signaling drives intrahepatic cholangiocarcinoma metastasis via GSK3β/β-catenin activation 5. Pozanicline, a nicotinic receptor ligand, represents a clinical approach targeting this pathway for smoking cessation.