CACUL1 and cancer: As an essential part of Cullin-RING E3 ubiquitin ligase (CRL), once neddylated, it will be activated by conformational changes to perform biological functions that trigger targeted protein ubiquitination and subsequent degradation (12, 13) and further regulate numerous biological processes, such as gene transcription, protein translation, cell division, cell cycle, signal transduction, and immune responses (14, 15), whereas dysfunction of the neddylation pathway leads to tumorigenesis and cancer progression due to disruption of Cullin neddylation (16, 17).