One or more lysosomal enzymes are defective in a large group of childhood storage diseases. The study of these disorders in cell culture has clarified the enzyme defect in six diseases, and revealed a pinocytotic mechanism for introducing hydrolytic enzymes into lysosomes of human fibroblasts. My experiments (Proc. Natl. Acad. Sci. USA (1977) 74, 2026-2030) suggest that lysosomal enzymes bear phosphohexosyl markers recognized by pinocytotic receptors on human fibroblasts. Further elucidation of the chemical details of the process of enzyme pinocytosis is planned. Inhibitor studies will be extended to further characterize the recognition markers. A search for appropriate intact cell systems capable of synthesizing large amounts of P32 labeled recognition markers attached to proteins will be followed by a radiochemical analysis of the marker. The site of modification and subsequent destinations of recognition marker bearing proteins will be determined. P32 labeled recognition marker will be used as a tool to evaluate the relative contribution of secretion/recapture and golgi derived primary lysosomes to the formation of secondary lysosomes. Possible defects in the synthesis of recognition marker bearing proteins in I-cell disease will be assessed. Already my experiments suggests that a unique type of protein modification previously supposed to be present only in lower organisms plays an important role in the localization of human lysosomal enzymes. Further study of the marker offers a fertile field for the discovery of novel activities and regulatory phenomena, for the development of technology for the treatment of lysosomal storage diseases and for the elucidation of genetic defects.