Different Pathways to the Lysosome: Sorting out Alternatives.

Considerable research supports a model in which hydrolytic enzymes of mammalian lysosomes are sorted to their destinations in a receptor-dependent mechanism. The ligand for the mammalian sorting receptors is mannose 6-phosphate (M6P). Two M6P receptors have been defined in mammals. Here, we review the foundational evidence supporting this mechanism and highlight the remaining gaps in our understanding of the mammalian mechanism, including evidence for M6P-independent sorting, and its relevance to lysosomal enzyme sorting in metazoa.