Biosynthesis of lysosomal proteinases in health and disease.

Proteolytic maturation of lysosomal proteinases is initiated after receptor-mediated targeting to prelysosomal compartments, while terminal processing occurs upon delivery to lysosomes. These late processing events are impaired in patients suffering from inherited lysosomal disorders, such as sialic acid storage disease and mucolipidosis II (I-cell disease). Lysosomes in the affected cells display marked changes in their physiological and morphological properties, with features reminiscent of prelysosomal compartments. This indicates that the absence of mature lysosomes interferes with the final processing steps during the biosynthesis of lysosomal proteinases. Thus, impaired proteinase maturation reflects an incompetent lysosomal apparatus and as such can be seen as a hallmark of lysosomal storage diseases.