Fig. 1

Dysregulation of the endocytic and autophagic pathways in LSDs including the NCLs. Cells import materials from outside the cell by endocytosis. This process is initiated by the invagination of the plasma membrane, which encloses the material forming the early endosome, which progresses to the late endosome. The fusion of the membranes of the late endosome and lysosome forms a hybrid structure called endolysosome. The fusion of the two membranes is catalyzed by Rab7, a small GTPase, and the endosomal cargo is degraded by lysosomal acid hydrolases and the constituent components are reutilized by the cell. The process of autophagy is initiated by the formation of a double-membrane structure in the cytoplasm called phagophore. This structure in its mature form is called phagosome, which encircles materials such as aged macromolecules and disabled organelles. The autophagosome fuses with the lysosome forming a hybrid structure called autolysosome. The lysosomal hydrolases then degrade the cargo to their respective components (i.e. amino acids for proteins, fatty acids for lipids, etc.) which are reutilized by the cells. Notably, impaired or missing lysosomal acid hydrolases or failure of endosome-lysosome and autophagosome-lysosome fusions may result in the accumulation of undigested cargo in the lysosome leading to lysosomal storage diseases