We will review i) known genetic lysosomal deficiencies in human patients that are associated with Parkinsonism or Parkinson's disease; ii) studies that examined lysosomal protein levels and activities in sporadic Parkinson's disease patients compared to normal controls; and iii) the most extensively studied lysosomal hydrolase, Cathepsin D, in relationship to protein aggregation and toxicity (Figure 2). The gene discussed is CTSD; the disease is Parkinson disease.