Given the complexity of the UPS and its essential functions in all organ systems, it is not surprising that it has been implicated in the pathophysiology of a large number of both congenital and acquired diseases and in the process of ageing itself.25,26 Several polymorphisms of the UPS and associated proteins have been described, the majority of which are disease-promoting.27,28 On the contrary, the p.S18Y polymorphism of the UCHL1 gene appears to confer at least a moderate protection in Parkinson's disease.29 Here, UCHL1 is linked to Parkinson disease.