Mutations in at least six genes, including alpha-synuclein, uchL1, LRRK2, parkin, PINK1, and DJ-1, are linked to Parkinson's disease. One vital question is how mutations in six different genes individually cause the same disease. Our goal is to determine whether these genes act on a common mechanism that contributes to the pathogenesis of Parkinson's disease. We are currently focus on defining the interactions between parkin, PINK1, and DJ-1 and roles of these interactions play in degradation of misfolded proteins. Results from this study will help to explain the molecular basis of recessive familial forms of Parkinson's disease and provide novel mechanisms for designing prevention and treatment strategies for the disease.