DCUN1D1 is a co-E3 ligase that promotes neddylation of cullin proteins in E3 cullin-RING ubiquitin ligase (CRL) complexes 1. The protein functions by binding cullin-RBX1 complexes in the cytoplasm and facilitating their nuclear translocation, enhancing recruitment of the E2-NEDD8 conjugate (UBE2M-NEDD8) and optimizing protein orientation for efficient NEDD8 transfer to cullin substrates 1. DCUN1D1 also relieves inhibitory effects of CAND1 on CRL assembly and activity 1. DCUN1D1 is significantly upregulated across multiple cancer types and functions as an oncogene. In prostate cancer, DCUN1D1 promotes proliferation and tumor growth through neddylation of CUL1, CUL3, CUL4A, and CUL5, with downstream deregulation of the Wnt/β-catenin pathway 2. In cervical cancer, DCUN1D1 is amplified at the 3q26 locus and enhances migration and invasiveness 34. In non-small-cell lung cancer, DCUN1D1 promotes metastasis by activating FAK signaling and upregulating PD-L1 5. In laryngeal squamous cell carcinoma, DCUN1D1 expression correlates with advanced disease stages and promotes cell proliferation, migration, and invasion through FAK and MMP-2 activation 6. Therapeutically, neddylation inhibition through DCN1 blockade shows promise in diverse diseases; selective inhibition of cullin3 neddylation alleviates renal fibrosis by promoting NRF2 accumulation and suppressing TGFβ-Smad signaling 7. Both DCUN1D1 and neddylation pathways represent potential druggable targets for cancer therapy 1.