To clarify the roles of USP22 and its main target H2Bub1 in cancers, it will be critical to assess the activity of the proteins responsible for both the addition and removal of the ubiquitin, which include not only USP22, but also the other DUBm members ATXN7, ATXN7L3 and ENY2, as well as RNF20 and RNF40. The gene discussed is RNF20; the disease is cancer.