CUE domain-containing 2 (CUEDC2) is a protein involved in the regulation of the cell cycle,inflammation,and tumorigenesis and is highly expressed in many types of tumors.CUEDC2 is phosphorylated by Cdk1 during mitosis and promotes the release of anaphase-promoting complex or cyclosome (APC/C) from checkpoint inhibition.CUEDC2 is also known to interact with IkB kinase α (IKKα) and IKKβ and has an inhibitory role in the activation of transcription factor nuclear factor-κB.Moreover,CUEDC2 plays an important role in downregulating the expression of hormone receptors estrogen receptorα and progesterone receptor,thereby impairing the responsiveness of breast cancer to endocrine therapies.In this review,current knowledge on the multi-functions of CUEDC2 in normal processes and tumorigenesis are discussed and summarized.