FBXW11 is an E3 ubiquitin ligase component of SCF complexes that regulates protein degradation through the ubiquitin-proteasome system. Primary substrates include β-catenin, TET2, YB1, IL-17RA, and SFPQ, which FBXW11 polyubiquitinates for proteasomal degradation 12345. FBXW11 functions as a contextual regulator: it acts as a tumor suppressor in hepatocellular carcinoma and chondrosarcoma by degrading oncogenic proteins, with reduced expression correlating with poor prognosis 36. Conversely, FBXW11 serves as an inflammatory biomarker in pancreatic disease, with elevated expression correlating with macrophage infiltration and NF-κB pathway activation 7. Gain-of-function FBXW11 mutations in salivary basal cell adenoma impair β-catenin binding, leading to Wnt/β-catenin pathway activation 1. FBXW11 expression is dynamically modulated during osteogenesis and dysregulated in cleidocranial dysplasia and osteosarcoma 8. Additionally, FBXW11-mediated degradation of TET2 promotes EGFR-TKI resistance in lung cancer through TNF/NF-κB signaling activation 2. Clinical significance includes potential as a prognostic biomarker and therapeutic target across multiple malignancies.