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. Here, MAP3K5 is linked to neoplasm.