Poly-ubiquitin chains are composed of ubiquitin monomers that are covalently linked through isopeptide bonds, which typically form between a lysine residue of one ubiquitin molecule and the C-terminal glycine residue of another ubiquitin molecule. Each human ubiquitin monomer is 76 amino acids (aa) in length and shares 96% and 100% aa identity with yeast and mouse ubiquitin, respectively. Seven of the 76 aa in ubiquitin are lysine residues that can participate in poly-ubiquitin chain formation. Linkage through specific lysine residues is thought to serve as a signal that affects protein degradation, signaling, trafficking and other cellular processes. Linkage-specific poly-ubiquitin chains are used to investigate mechanisms of chain recognition, binding and hydrolysis by the proteasome, deubiquitinating enzymes, E3 ligases or other proteins that contain ubiquitin-associated domains (UBAs) or ubiquitin-interacting motifs (UIMs). Lys63-linked poly-ubiquitin has been implicated in several non-degradative processes such as receptor endocytosis and sorting, translation, DNA damage repair, the stress response and signaling in the NFκB pathway.