NUCLEOLIN and frontotemporal dementia: GRN-mutant neurons from an FTD patient also showed decreased activity of the lysosomal enzyme cathepsin D via a loss of the PGRN cleavage product, cathepsin E. Interestingly, homozygous GRN and CTSD, which encodes for cathepsin D, mutations lead to a similar form of NCL [142–144], suggesting this functional relationship may provide a possible mechanism for the overlapping NCL-like pathology observed in GRN-neurodegeneration.