Schematic representation of CI-MPR trafficking in the cells. CI-MPR follows different routes, including the biosynthetic pathway from the trans-Golgi network (TGN), where it binds and delivers newly synthesized lysosomal hydrolases to the late endosomal compartment. A fraction (approximately 10%) of CI-MPR is located on the cell surface, where it mediates the uptake of lysosomal enzymes, is internalized in the endocytic pathway and recycles through the endocytic recycling compartment (ERC), again to the plasma membrane. The finding of increased co-localization of CI-MPR with LC3 in Pompe disease (PD) fibroblasts indicates that in these cells part of the CI-MPR is diverted from its normal routes and is sequestered in autophagosomes and autophagolysosomes. Since transferrin and transferring receptor trafficking is not affected in PD fibroblasts, it is likely that the disruption of CI-MPR trafficking occurs at the late endosomal compartment and in the retrograde route to the TGN.