In line with this, we show that the inhibition of the enzymatic activity of the most abundant lysosomal hydrolases CTSD, CTSB, and CTSL [22], by chemical compounds, enhances the formation of soluble αSyn in H4 cells and PD patient-derived DA neurons harbouring αSyn triplication (Additional file 1: Fig. S8a–d) as well as insoluble αSyn forms in PD iPS-DA neurons (3 × SNCA) (Additional file 1: Fig. S8e, f). This evidence concerns the gene CTSL and Parkinson disease.