FBXO45 is a substrate-recognition component of SCF E3 ubiquitin ligase complexes that regulates protein degradation through the ubiquitin-proteasome system 1. The protein functions as an oncogene in multiple cancer types, promoting tumorigenesis through diverse mechanisms. In pancreatic cancer, FBXO45 facilitates progression by targeting tumor suppressor USP49 for ubiquitination and degradation 2. In lung cancers, FBXO45 is overexpressed and associated with poor prognosis, promoting metastasis and the Warburg effect while reducing ferroptosis through stabilization of ZEB1 by inhibiting its ubiquitination 34. In hepatocellular carcinoma with TP53 mutations, FBXO45 drives lung metastasis by promoting TFG ubiquitination and activating the ATF2-NF-κB pathway 5. Beyond cancer, FBXO45 plays roles in HIV-1 regulation by promoting Tat ubiquitination and SQSTM1/p62-mediated autophagic degradation, thereby restricting viral replication 6. In diabetic endothelial dysfunction, FBXO45 mediates GPX4 ubiquitination leading to oxidative stress 7. FBXO45 also regulates germinal center formation and B-cell lymphomagenesis through control of GEF-H1 8. These diverse functions establish FBXO45 as a critical regulator of cellular homeostasis and a potential therapeutic target across multiple diseases.