In this study, our results clearly showed that high OTUD1 expression is closely correlated with poor prognosis and that a region spanning amino acids 105–164 is capable of mediating OTUD1 self-assembly both in vitro and in vivo, an event that is needed for OTUD1-associated aggresome formation, ASK1 stabilization, tumor cell stemness maintenance and tumorigenesis, underscoring the importance of the disordered OTUD1 N-terminal region in the regulation of characteristic cancer signaling pathways and reinforcing the idea that OTUD1 is an oncogene in ovarian cancer. This evidence concerns the gene MAP3K5 and ovarian carcinoma.