GRN and frontotemporal dementia: Multiple studies have demonstrated that PGRN deficiency leads to the upregulation of lysosomal gene expression and protein level, impaired clearance of autophagosomes, and TDP-43 aggregation in the brains of FTD-GRN patients and in mouse and cellular models [14, 16–18, 36, 38, 40, 44, 55–57].