Mutations in the parkin gene cause autosomal recessive inherited juvenile parkinsonism (ARJP) and account for the majority of cases of inherited Parkinson's disease (PD) of young onset (<45 years of age). Patients with parkin mutations commonly have atypical clinical features such as dystonia at onset, hyper-reflexia, diurnal fluctuations, and sleep benefit; however, parkin mutation patients with both typical PD symptoms and older age of onset have been identified. Parkin is a ubiquitin protein ligase (E3), a component in the pathway that attaches ubiquitin to specific proteins, designating them for degradation by the proteasome. Several substrates for parkin have been identified (CDCrel-1, o-glycosylated alpha-synuclein, parkin associated endothelin-like cell receptor, and synphilin). The role of these substrates in the pathogenesis of ARJP is under active study. Most patients with parkin mutations lack Lewy bodies, suggesting that functional parkin is involved in the formation of these highly ubiquitinated inclusions. Furthermore, the recognition that parkin mutations can lead to a disorder clinically similar to sporadic PD, but presumably lacking Lewy bodies, calls into question the necessity of Lewy bodies for the diagnosis of PD and nigral cell death. Studies of parkin are increasing the focus on the role of the ubiquitin-proteasome system in the pathogenesis of both familial and sporadic PD.