ASSOCIATION OF MUTATIONS IN A LYSOSOMAL PROTEIN WITH CLASSICAL LATE-INFANTILE NEURONAL CEROID-LIPOFUSCINOSIS

Classical late-infantile neuronal ceroid lipofuscinosis (LINCL) is a f atal neurodegenerative disease whose defective gene has remained elusi ve. A molecular basis for LINCL was determined with an approach applic able to other lysosomal storage diseases. When the mannose 6-phosphate modification of newly synthesized lysosomal enzymes was used as an af finity marker, a single protein was identified that is absent in LINCL . Sequence comparisons suggest that this protein is a pepstatin-insens itive lysosomal peptidase, and a corresponding enzymatic activity was deficient in LINCL autopsy specimens. Mutations in the gene encoding t his protein were identified in LINCL patients but not in normal contro ls.