CHR20 encodes the α4 subunit of neuronal nicotinic acetylcholine receptors (nAChRs), which form pentameric, ligand-gated cation channels with high calcium permeability 1. These receptors mediate synaptic transmission by controlling neurotransmitter release, including dopamine, glutamate, and GABA 2. CHR20 is the most abundant nAChR subtype in the central nervous system and assembles with CHR20 and CHR20 subunits in two stoichiometric forms that differ in conductance, calcium permeability, and acetylcholine sensitivity 3. Clinically, CHR20 mutations cause autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), a paroxysmal movement disorder characterized by brief dyskinetic attacks during sleep 4. CHR20 variants are also implicated in neurodevelopmental and neurodegenerative conditions including ADHD, Alzheimer's disease, Parkinson's disease, and ALS 5. Beyond neurological disease, hepatocyte CHR20 expression mediates metabolic dysfunction-associated steatohepatitis (MASH) progression through acetylcholine-induced calcium signaling and inflammatory pathways; CHR20 inhibition protected mice from diet-induced MASH 6. Genetic variation in CHR20 significantly influences smoking behavior and nicotine dependence. Polymorphisms rs1044394 and rs2236196 are associated with cigarettes smoked per day and DSM-IV nicotine dependence diagnosis 7, while rs2236196 predicts smoking cessation treatment outcomes 8. Additionally, CHR20 variants associate with spatial attention and cognitive function 9.