Ubiquitination has been found to have vital roles in cellular processes including proteasomal degradation, endocytosis, DNA repair, cell cycle regulation, and gene expression. For example, monoubiquitination of cell surface transmembrane receptors target them for endocytosis, and polyubiquitine chains act as scaffolds for ubiquitin-binding proteins, and target them for proteolytic degradation by proteasome. Therefore, when the ubiquitination process is not under proper control, the protein degradation system can be hugely affected, causing protein accumulation and aggregation, which leads to a wide range of human diseases, such as cancer, diabetes, and cardiovascular and neurodegenerative diseases, including Alzheimer’s, Huntington’s and prion diseases.