We generated novel cellular models for all known LSDs by engineering cell lines using the CRISPR-Cas9 technology. In this year, we obtained a set of 18 different cell lines. A preliminary characterization revealed that most of the cell lines generated using this approach, reproduce the disease phenotypes. These cell lines show lysosomal dysfunction, that is a typical hallmark of LSDs. This dysfunction was rescued by reintroducing the wild type gene. We also performed multiparametric experiment for the simultaneous analysis of lysosomal morphology and function, demonstrating that these cell lines are suitable for drugs screening experiments. The generation of a new LSDs Biobank (LSD-CRIB) showed that these new cells lines are a powerful tool to perform comparative and mechanistic studies of lysosomal physiology, dynamics, positioning. Moreover, we demonstrated that these cell lines can be used for drug screening approaches.