Mutations of the α-synuclein gene, have been identified in some familial forms of Parkinson's disease, and α-synuclein protein has been shown to accumulate in the brains of patients with the disease. These findings suggest that Parkinson's disease may be caused by the abnormal aggregation of α-synuclein protein. Here we have identified in a German family with Parkinson's disease a missense mutation in the ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) gene. We show that this mutation, Ile93Met, causes a partial loss of the catalytic activity of this thiol protease, which could lead to aberrations in the proteolytic pathway and aggregation of proteins.