AD, the most frequent neurodegenerative disorder, is characterized by extracellular deposition of amyloid plaques and intracellular tangles, composed by aggregated Aβ peptides and hyperphosphorylated protein tau [65], paralleled by a robust activation of lysosomal-mediated proteolysis, albeit displaying defects in execution [38,66,67]. Here, MAPT is linked to Alzheimer disease.