Transmembrane protein 106B (TMEM106B)

Transmembrane protein 106B (TMEM106B) is a type II integral membrane protein localized predominantly to lysosomal membranes, with its N-terminus facing the cytosol and its glycosylated C-terminus facing the lysosomal lumen. It is composed of 274 amino acids and highly expressed in neurons and oligodendrocytes within the central nervous system. TMEM106B plays a crucial role in maintaining lysosome size, trafficking, and acidic pH, as well as proteolytic processing and myelination, especially through interactions with MAP6 and cathepsin D. Genetic variants and dysregulation of TMEM106B have been linked to several neurodegenerative diseases, particularly frontotemporal lobar degeneration with TDP-43 pathology, as well as to lysosomal storage and myelination disorders. It is currently under investigation as a therapeutic and biomarker target, but no approved drugs directly target TMEM106B. Safety concerns for modulation of this protein revolve around maintaining proper lysosomal function and avoiding detrimental cell stress or death.

Other names

TMEM106BTransmembrane protein 106BType II transmembrane protein 106B

Not established for clinical drugs (mechanistic studies target proteolytic processing, trafficking, and pH modulation; no approved drugs yet)