Dysregulation of the ubiquitin–proteasome system including the positive or negative regulation of E3 ligases, DUBs, or proteasomes seriously affects cellular homeostasis and causes the development of serious pathologic conditions, such as tumor suppression or promotion in cancer, protein accumulation in neurodegenerative diseases, and forming an ineffective immune response in the body (Figure 3). This evidence concerns the gene UBA52 and neurodegenerative disease.