FBXL7 is a substrate recognition component of SCF ubiquitin-protein ligase complexes that regulates protein degradation across multiple cellular processes 1. As an F-box protein, FBXL7 mediates polyubiquitination and proteasomal degradation of diverse substrates including AURKA, BIRC5, c-SRC, Snail1, and PFKFB4, thereby controlling cell cycle progression, apoptosis, and metabolic pathways 2345. Clinically, FBXL7 functions primarily as a tumor suppressor. Reduced FBXL7 expression correlates with poor prognosis across multiple cancers including pancreatic, prostate, and glioma 36. Low FBXL7 levels promote epithelial-mesenchymal transition and metastasis by impairing c-SRC and Snail1 degradation 34. In non-small cell lung cancer, hypoxia-induced suppression of FBXL7 expression through the EZH2 pathway enhances glucose metabolism and tumor growth 5. Conversely, FBXL7 downregulation in hepatocellular carcinoma affects immune tolerance through PTEN-mediated metabolic reprogramming 7. FBXL7 promoter hypermethylation occurs frequently in pancreatic and prostate cancers 3, while body hypomethylation shows biomarker potential in upper aerodigestive tract tumors 8. Restoring FBXL7 expression or inhibiting its upstream regulators represents a promising therapeutic strategy 65.