DCUN1D5 (defective in cullin neddylation 1 domain containing 5) is a key regulatory protein that facilitates the neddylation of cullin proteins, which is essential for activating cullin-RING E3 ubiquitin ligases (CRLs) 123. The protein transfers NEDD8 from N-terminally acetylated NEDD8-conjugating E2 enzymes to cullin C-terminal domain-RBX complexes. DCUN1D5 is significantly overexpressed across multiple cancer types, including triple-negative breast cancer, osteosarcoma, lung adenocarcinoma, and colorectal cancer, where it promotes tumor progression through various pathways 4567. In breast cancer, DCUN1D5 activates the FN1/PI3K/AKT pathway and is transcriptionally regulated by YY1 4. The protein enhances cellular proliferation, migration, invasion, and contributes to chemotherapy resistance, particularly cisplatin resistance in osteosarcoma 5. Additionally, DCUN1D5 plays a role in DNA damage response, with expression decreasing after genotoxic stress and knockdown leading to cell cycle arrest and increased apoptosis 8. High DCUN1D5 expression correlates with poor prognosis across multiple cancer types, suggesting its potential as both a prognostic biomarker and therapeutic target 456.