PGRN also regulates lysosomal function by acting as a chaperone for lysosomal enzymes including cathepsin D. Heterozygous loss-of-function PGRN gene (GRN) mutations cause frontotemporal lobar degeneration (FTLD) with accumulation of transactivation response DNA-binding protein 43 (TDP-43) by reducing more than 50% of PGRN protein levels. This evidence concerns the gene GRN and frontotemporal dementia.