GRN and neurodegenerative disease: Additional support for our data comes from a study of PTV:PGRN, a brain-penetrant form of hPGRN, that was efficacious weeks after dosing Grn−/− mice, when PGRN has been degraded, suggesting that stable, lysosomal GRNs mediate prolonged efficacy.63 These findings suggest that GRNs have a central role in regulating lysosomal function and lysosomal lipid metabolism and may hold therapeutic potential for neurodegenerative diseases with lysosome dysfunction.73–75