FBXO11 (F-box protein 11) functions as a substrate recognition component of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-ligase complex, mediating proteasomal degradation of multiple target proteins including DTL, BCL6, SNAI1, and CIITA 12. In B cell biology, SCF(FBXO11) catalyzes BCL6 degradation, facilitating germinal center B cell terminal differentiation toward memory and plasma cells [UniProt summary]. The complex regulates TGF-β signaling, cell migration, and cell-cycle progression through DTL degradation [UniProt summary]. FBXO11 also mediates MHC class II expression by targeting CIITA for proteasomal degradation, with therapeutic implications for enhancing anti-tumor immune responses in acute myeloid leukemia 2. In prostate cancer, FBXO11 cooperates with NDR1 kinase to phosphorylation-dependently ubiquitinate β-catenin, suppressing epithelial-mesenchymal transition and metastasis 3. Additionally, FBXO11 mediates hnRNPA2B1 degradation within the CAND1-SCF(FBXO11)-hnRNPA2B1 axis regulating hepatocellular carcinoma lipid metabolism 4. Clinically, de novo FBXO11 variants cause intellectual developmental disorder with dysmorphic facies and behavioral abnormalities, featuring intellectual disability, autism spectrum disorder, and characteristic facial features including a thin upper lip 15.