C99-intermediated endolysosomal impairment was shown in the iPSC of humans, resulting in embracing AD-related PS1 or APP mutations demonstrating an endogenous APP transcript [76,80,81], and thus demonstrating that weakened autophagic-lysosomal tasks are not an object owing to a burden of mutated C99 or APP portions in upregulated models. The gene discussed is PSEN1; the disease is Alzheimer disease.