The present disclosure provides technologies relating to lysosomal activation. The disclosure provides several strategies for increasing level and/or activity of lysosomal enzyme, and furthermore demonstrates the surprising applicability of such strategies in the treatment and/or prophylaxis of certain proteinopathies. Among other things, the present invention provides methods and compositions for the treatment and/or prophylaxis of proteinopathies other than lysosomal storage diseases through lysosomal activation. In particular, the present disclosure provides methods and compositions for the treatment and/or prophylaxis of neurodegenerative proteinopathies, and in particular those associated with accumulation of a-synuclein. The present disclosure specifically provides methods and compositions for the treatment and/or prophylaxis of Parkinson's disease.
