TMEM35A (also known as NACHO) is a molecular chaperone protein essential for nicotinic acetylcholine receptor (nAChR) assembly and trafficking in the brain. Primary Function: TMEM35A mediates proper folding, assembly, and surface trafficking of multiple nAChR subtypes including α7, α4-β2, α3-β2, α3-β4, and α6-β2 receptors 1234. Mechanism: The protein functions as a chaperone within the endoplasmic reticulum, stably associating with components of the oligosaccharyl transferase complex and calnexin to facilitate nAChR subunit assembly at early stages 3. TMEM35A also regulates stoichiometric assembly, promoting the α4(2):β2(3) form over alternative configurations 5. Disease Relevance: Complete knockout of TMEM35A eliminates α7nAChR surface expression in mouse brain 4. In Alzheimer's disease, dysregulation of NACHO-Ly6h balance promotes pathological α7-mediated calcium influx and neurotoxicity 6. Clinical Significance: TMEM35A-dependent nAChR dysfunction contributes to airway pathology, with chaperone expression elevated in asthma and linked to nicotine-induced endoplasmic reticulum stress and airway smooth muscle proliferation 7. These findings suggest TMEM35A may represent a therapeutic target for neurological and pulmonary conditions involving nAChR dysfunction.