FBXO22 is an F-box protein component of the SCF-type E3 ubiquitin ligase complex that serves as a key substrate-recognition unit for proteasomal protein degradation 1. It regulates multiple cellular processes through selective protein degradation. FBXO22 targets BACH1, a pro-metastatic transcription factor, for degradation under heme-rich conditions and oxidative stress, with reactive oxygen species modifying BACH1 cysteine residues to expose its degron 23. The protein also degrades nuclear (but not cytoplasmic) PTEN at lysine 221, promoting tumorigenesis 4, and ubiquitinates p21, a cell cycle inhibitor, supporting hepatocellular carcinoma progression 1. In acute myeloid leukemia, FBXO22 promotes leukemogenesis by targeting BACH1 for degradation 5. Additionally, FBXO22 facilitates targeted protein degradation strategies through cysteine residues (C227/C228, C326), enabling therapeutic degradation of oncogenic proteins including NSD2 and BRD4 67. CNVs involving FBXO22 region (15q24.2q24.5) are associated with neurodevelopmental phenotypes 8. High FBXO22 expression correlates with poor prognosis in multiple cancers and serves as an independent prognostic indicator.