Transmembrane protein 35A (TMEM35A)

Transmembrane protein 35A (TMEM35A), also known as NACHO (novel acetylcholine receptor chaperone), is a small neuronal transmembrane molecular chaperone essential for the assembly, folding, and functional membrane trafficking of nicotinic acetylcholine receptors (nAChRs), especially the homomeric α7 subunit as well as heteromeric α3, α4, and α6-containing subtypes[1][2][4][6]. TMEM35A is expressed predominantly in neurons and is necessary for proper nAChR function across the brain and spinal cord. Loss of TMEM35A in mice leads to disruption of α7 nAChR expression, increased pain sensitivity, neuroinflammation, and changes in gene expression profiles in the nervous system, implicating it in mechanisms of nociception, neurodevelopment, and potentially neurodegenerative and developmental diseases[1][3][4][6]. TMEM35A does not bind classic nAChR ligands directly but is required for their assembly and trafficking, making it a putative therapeutic target for disorders linked to nAChR dysfunction such as neuropathic pain, cognitive disorders, and epilepsy[1][4][6]. Although small-molecule or biologic modulators directly targeting TMEM35A are not yet clinically developed, its essential chaperone role underlies its therapeutic relevance[1][4][6].

Other names

NACHONovel acetylcholine receptor chaperoneTMEM35FLJ14084TUF-1nAChR regulatornicotinic acetylcholine receptor regulatortransmembrane protein 35

Modulation of nicotinic acetylcholine receptor (nAChR) function via chaperoning their assembly and membrane trafficking; drugs targeting TMEM35A act indirectly by modulating nAChR activity