The ubiquitin-proteasome system (UPS) is a major intracellular protein degradation system in eukaryotes. Damaged, misfolded, or superfluous proteins are labeled with multiple ubiquitin molecules (a 76 amino acid peptide) via the sequential action of E1 activating enzyme, E2 conjugating enzyme, and E3 ligase ultimately leading to destruction of the protein by the 26S proteasome. Deubiquitinases cleave the bond between ubiquitin and protein. Dysregulation of the UPS and/or DUBs is implicated in many neurological disorders, cancer, atherosclerosis and other pathological states.