In AD, PD, and HD, two important protein degradation systems, the autophagy system and ubiquitin proteasome system (UPS), have been reported to be dysfunctional during the progression of diseases and result in the formation of disease protein aggregates, including amyloid precursor proteins (APP) in AD, α-synuclein in PD, and Huntingtin in HD (Figure 3). The gene discussed is HTT; the disease is Alzheimer disease.