Fig. 2

The physiological roles of TMEM106B under healthy conditions. TMEM106B is a type II transmembrane protein located on late endosome and lysosome, which has 274 residues and three structural domains. This C-terminal fragment (118–274 residue) contains five important N-glycosylation sites (N145, N151, N164, N183, N256). Proteins with known interaction with N-terminal TMEM106B are circled in red and C-terminus in blue. TMEM106B interacts with AP1 and v-ATPase V0 domain subunits, which controls the acidification of lysosomes. The interaction with MAP6 regulates lysosome retrograde transport. TMEM106B further activates TFEB-dependent lysosome biogenesis. Lysosomal activity is significantly modulated by intraluminal pH in addition to enzyme concentration and lysosome location within the cell to correctly degrade the contents. Endosome and lysosome fusion is also mediated by TMEM106B. TMEM106B plays important roles in the transportation, maturation and biogenesis of lysosomes. TMEM106B regulates lysosome traffic and exocytosis to affect PLP to be transported to the myelin sheath in oligodendrocytes