Although the precise mechanism that causes GPNMB upregulation in progranulin deficiency is unclear, our data suggest that measurement of GPNMB levels in the CSF could be used to monitor changes in microglial activation and response to therapies in FTD-GRN patients, similar to substrate reduction therapy in lysosome storage disorders [71, 78, 119]. Here, GPNMB is linked to frontotemporal dementia.