UBR7 is an E3 ubiquitin ligase that functions primarily through histone H2B monoubiquitination at lysine 120 (H2BK120ub) 1. As a component of the N-end rule pathway, UBR7 recognizes substrates via its plant homeodomain (PHD) finger 2, though it also catalyzes non-histone protein ubiquitination 3. Beyond its canonical E3 ligase role, UBR7 functions as a histone chaperone that modulates post-nucleosomal histone H3 complexes and their reincorporation into chr14 4. UBR7 acts as a broad-spectrum tumor suppressor across multiple cancer types. In hepatocellular carcinoma, UBR7 inhibits glycolysis by suppressing HK2 expression through the Keap1/Nrf2/Bach1 axis 2. In triple-negative breast cancer, UBR7 loss promotes epithelial-to-mesenchymal transition and metastasis via reduced H2BK120ub on cell adhesion genes 1. UBR7 cooperates with EZH2 to suppress TGF-β signaling and extracellular matrix remodeling in TNBC 5. In pancreatic ductal adenocarcinoma, the UBR7-PRMT5 axis regulates gemcitabine resistance through glycolytic reprogramming 6. Additionally, UBR7 suppresses HBV-induced HCC by ubiquitinating Sp110, thereby inhibiting interferon-β immune signaling 3. UBR7 mutations cause Li-Campeau syndrome, a neurodevelopmental disorder with global developmental delay and autosomal recessive inheritance 7.