NUB1 (negative regulator of ubiquitin-like proteins 1) is an interferon-inducible protein that functions as a critical negative regulator of the NEDD8 conjugation system 1. Mechanistically, NUB1 recruits NEDD8, UBD/FAT10, and their conjugates to the proteasome for degradation by trapping unfolded FAT10 in its N-terminal ubiquitin-like domain and delivering it to the 26S proteasome in a ubiquitin-independent manner 2. This process involves formation of a dynamic complex with the proteasomal Rpn1 subunit, enabling ATP-dependent degradation 2. NUB1 exhibits tumor-suppressive properties across multiple cancer types. In gastric cancer, NUB1 overexpression inhibits proliferation and invasion by upregulating p27Kip1 and suppressing epithelial-mesenchymal transition 3. In hepatocellular carcinoma, reduced NUB1 promotes tumor growth by failing to suppress NEDD8-mediated PCNA NEDDylation, which stabilizes PCNA and antagonizes its polyubiquitination 4. Beyond cancer, NUB1 upregulation is associated with pro-apoptotic responses in ischemic acute kidney injury 5 and dysregulated neddylation in rheumatoid arthritis, where NUB1 overexpression decreases NF-κB activation and inflammatory responses in fibroblast-like synoviocytes 6. These findings position NUB1 as a potential biomarker and therapeutic target 1.