TMEM175: A lysosomal ion channel associated with neurological diseases

• Published in: Neurobiology of disease 2023-09, Vol.185, p.106244-106244, Article 106244
• Main Authors: Wu, Luojia, Lin, Yue, Song, Jiali, Li, Longshan, Rao, Xiuqin, Wan, Wei, Wei, Gen, Hua, Fuzhou, Ying, Jun
• Format: Article
• Language: English
• Subjects: Autophagy; Ion channel; Lysosomal membrane protein; Lysosome; Neurological disease; TMEM175
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2023.106244

Lysosomes are acidic intracellular organelles with autophagic functions that are critical for protein degradation and mitochondrial homeostasis, while abnormalities in lysosomal physiological functions are closely associated with neurological disorders. Transmembrane protein 175 (TMEM175), an ion channel in the lysosomal membrane that is essential for maintaining lysosomal acidity, has been proven to coordinate with V-ATPase to modulate the luminal pH of the lysosome to assist the digestion of abnormal proteins and organelles. However, there is considerable controversy about the characteristics of TMEM175. In this review, we introduce the research progress on the structural, modulatory, and functional properties of TMEM175, followed by evidence of its relevance for neurological disorders. Finally, we discuss the potential value of TMEM175 as a therapeutic target in the hope of providing new directions for the treatment of neurodegenerative diseases. •TMEM175 is a highly permeable ion channel for both protons and potassium ions in the lysosomal membrane.•TMEM175 affects lysosomal autophagy by regulating intra-lysosomal acidity and alkalinity.•TMEM175 mutation is a high-risk factor for neurodegenerative disease.