Recent work shows that the 20S proteasome can degrade intrinsically disordered proteins such as α-synuclein via ubiquitin-independent mechanisms [41], particularly under oxidative stress and aging conditions [42], advising that impairment of the UPS system in PD may increase reliance on alternative degradation pathways, which, if insufficient, could contribute to α-synuclein accumulation. Here, SNCA is linked to Parkinson disease.