APP and Parkinson disease: As CTSD is highly expressed in neuronal cell lines (Supplementary Figure 1B), where it degrades disease-associated substrates like a-syn and APP (Zhou et al., 2006; Sevlever et al., 2008; Cullen et al., 2009), we analyzed PD-associated CTSD variants in SH-SY5Y (Figure 2) as well as H4 cells (Figure 3) deficient for CTSD (CTSD KO).