FBXO4 (F-box protein 4) functions as a substrate recognition component of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex, mediating the ubiquitination and subsequent proteasomal degradation of multiple target proteins 1. The protein operates through formation of a homodimeric SCF complex structure that facilitates substrate recognition and degradation 1. Key substrates include cyclin D1, FXR1, hnRNPK, β-catenin, and MCL-1, which regulate critical cellular processes including cell cycle progression, apoptosis, and differentiation 234. FBXO4 functions as a tumor suppressor by restricting oncogenic activities: it limits hnRNPK-mediated translation of oncogenes like c-Myc through K63-linked polyubiquitination 3, degrades FXR1 to suppress tumorigenesis in head and neck squamous cell carcinoma 2, and inhibits Wnt/β-catenin signaling by degrading β-catenin 4. Clinical significance is evident as FBXO4 is downregulated in various cancers including papillary thyroid cancer, where its restoration suppresses migration, invasion, and promotes apoptosis 5. Additionally, FBXO4 regulates HPV E6 oncoprotein stability and can induce p53-dependent cell death in HPV-positive cervical cancer cells 6. The protein's tumor suppressor functions make it a potential therapeutic target for cancer treatment 7.