The ubiquitination of proteins is catalyzed by the activities of three enzymes called ubiquitin-activing enzyme (E1), ubiquitin-conjugating enzyme (E2), and ubiquitin ligase (E3) [353]. PARK2, encoding Parkin, a ubiquitin E3 ligase, causes juvenile-onset recessive PD (before 40 years of age) [328] with relatively confined neuronal loss in the SNc and locus coeruleus, but with an absence of LBs. Several substrates of Parkin have been identified, including α-Syn, synphilin-1 and other synaptic proteins [356]. Mutations in the parkin gene result in a loss-of-function of E3, thus possibly causing some substrates of Parkin to accumulate and aggregate within cells. One parkin mutation found in a Turkish patient (Gln-311→X), replacing a glutamine residue at position 311 with a stop codon), causes a C-terminal truncation of 155 amino acids of Parkin [357].