The article reviews the structure and function of mammalian nicotinic acetylcholine receptors (nAChRs), highlighting their role in various physiological processes and diseases. It begins with the historical context of nAChR discovery, starting with Langley's work on nicotine's effects on nerve endings. The article discusses the classification of AChRs into metabotropic muscarinic and ionotropic nicotinic receptors, emphasizing the latter's role in ion channel gating. The muscle nAChR was the first characterized, and its structure was elucidated through studies of the Torpedo electric organ and α-bungarotoxin. The nAChR is a pentameric protein with a conserved extracellular domain, three transmembrane domains, and a cytoplasmic loop. The Cys-loop is crucial for agonist binding and receptor function. The article details the diversity of nAChR subunits, including α and non-α subunits, and their expression in various tissues. It also explores the ligand-binding site, channel gating mechanisms, and the importance of subunit diversity in determining receptor function. The article discusses the evolutionary conservation of nAChRs and their role in predator-prey interactions, with examples like nicotine and α-bungarotoxin. It also covers the regulation of nAChR expression through transcriptional control, gene duplication, and the influence of environmental factors. The review concludes with the significance of nAChR diversity in neuronal and non-neuronal functions, emphasizing the need for further research to understand their roles in health and disease.The article reviews the structure and function of mammalian nicotinic acetylcholine receptors (nAChRs), highlighting their role in various physiological processes and diseases. It begins with the historical context of nAChR discovery, starting with Langley's work on nicotine's effects on nerve endings. The article discusses the classification of AChRs into metabotropic muscarinic and ionotropic nicotinic receptors, emphasizing the latter's role in ion channel gating. The muscle nAChR was the first characterized, and its structure was elucidated through studies of the Torpedo electric organ and α-bungarotoxin. The nAChR is a pentameric protein with a conserved extracellular domain, three transmembrane domains, and a cytoplasmic loop. The Cys-loop is crucial for agonist binding and receptor function. The article details the diversity of nAChR subunits, including α and non-α subunits, and their expression in various tissues. It also explores the ligand-binding site, channel gating mechanisms, and the importance of subunit diversity in determining receptor function. The article discusses the evolutionary conservation of nAChRs and their role in predator-prey interactions, with examples like nicotine and α-bungarotoxin. It also covers the regulation of nAChR expression through transcriptional control, gene duplication, and the influence of environmental factors. The review concludes with the significance of nAChR diversity in neuronal and non-neuronal functions, emphasizing the need for further research to understand their roles in health and disease.