FBXO17 (F-box protein 17) functions as a substrate recognition component of SCF-type E3 ubiquitin ligase complexes 1. As an F-box protein, FBXO17 specifically recognizes and targets glycoproteins with complex-type oligosaccharides and sulfated glycans for proteasomal degradation 1, though the precise molecular details of substrate binding remain incompletely characterized in the provided literature. Mechanistically, FBXO17 mediates ubiquitination of GSK3β at lysine 183, promoting its K48-linked polyubiquitination and degradation 1. This activity negatively regulates inflammatory responses by reducing GSK3β-dependent cytokine production in lung epithelial cells 1. Additionally, FBXO17 activates the Akt/ERK signaling pathways, enhancing cell proliferation and metabolic activity 2. Clinically, FBXO17 dysregulation is associated with multiple malignancies. In high-grade glioma, elevated FBXO17 expression correlates with significantly shorter overall survival independent of IDH1 mutation status 3, and promotes glioma progression through glycolysis pathway activation and Akt/GSK-3β/Snail signaling 45. FBXO17 similarly promotes lung adenocarcinoma and renal cell carcinoma progression 26. Furthermore, FBXO17 expression can be regulated by promoter methylation, suggesting epigenetic therapeutic potential 3. FBXO17 transcript expression may also involve human endogenous retrovirus integration and influence interferon-mediated viral immune responses 7.