Catabolism of N-glycoproteins in mammalian cells: Molecular mechanisms and genetic disorders related to the processes.

N-glycans on glycoproteins serve as one of the most important co- and post-translational modifications of proteins, and it has been well established that they play pivotal roles in controlling the physicochemical and/or physiological properties of the carrier proteins. The biosynthetic/processing pathways for N-glycans have been well characterized in mammalian cells. There are, however, issues that remain to be clarified concerning aspects of their degradation. While the molecular mechanism of the lysosomal degradation for N-glycoproteins has been well studied in relation to genetic disorders, which are collectively referred to as lysosomal storage disorders, evidence exists to suggest that there are also "non-lysosomal" degradation processes, which are now known to occur widely in eukaryotic cells. In this review, our current knowledge of the lysosomal/non-lysosomal degradation of N-glycoproteins in mammalian cells, as well as in human genetic disorders caused by the defects of these processes, is reviewed.