The eventual permeability of lysosomes and the release of cathepsins to the cytosol could lead to mitochondrial damage and promote lysosome dysfunction and cellular death in these tissues, where the overall evidence is not yet conclusive and more studies are needed to clarify how dysregulated cathepsins mediate lysosome defects in obesity, NPC, and Gaucher diseases. This evidence concerns the gene CTSS and obesity due to melanocortin 4 receptor deficiency.