Mutations in the progranulin (PGRN) encoding gene, GRN, cause familial frontotemporal dementia (FTD) and neuronal ceroid lipofuscinosis and is also implicated in Parkinson’s disease. These mutations result in decreased PGRN expression. PGRN is highly expressed in peripheral immune cells and microglia and regulates cell growth, survival, repair, and inflammation. As well, PGRN is implicated in regulating lysosome function, however, the exact role of PGRN in lysosomal function and how this contributes to inflammation and degeneration is not entirely understood. To better understand the role of PGRN in regulating lysosome function, I want to examine how loss of GRN impacts lysosomal and cathepsin activity. I have previously demonstrated that Grn-/- MEFs exhibit increased pan-cathepsin activity relative to Grn+/+ MEFs, and significantly impacts expression of LAMP1. The significant increase in pan-cathepsin activity in the Grn-/- MEFs confirms that PGRN loss does alter cathepsin activity, which may be a result of compensatory mechanism(s) happening within the cell. I want to expand this investigation by knocking progranulin back into Grn-/- MEFs and reassessing pan-cathepsin activity and LAMP1 expression.