Reduced protein stability of human DJ-1/PARK7 L166P, linked to autosomal recessive Parkinson disease, is due to direct endoproteolytic cleavage by the proteasome

► DJ-1/PARK7 mutations have been linked with a familial form of early onset PD. ► DJ-1 wild type and the missense mutants M26I, R98Q, A104T and D149A are stable proteins in the cell. ► DJ-1 L166P mutant is unstable because of its direct endoproteolytic degradation by the proteasome. ► Genetic evidence obtained in yeast shows the direct role of proteasome in degradation of DJ-1 L166P.