FBXW12 is an F-box protein that functions as a substrate-recognition component of SCF-type E3 ubiquitin ligase complexes 1. Its primary function is promoting degradation of the interleukin-22 receptor subunit IL22RA1 through ubiquitin-mediated proteasomal degradation in both resting and IL-22-stimulated conditions 1. FBXW12 acts as a cell growth suppressor; its knockdown increases epithelial cell proliferation and enhances STAT3 phosphorylation and mitogen-activated protein kinase signaling 1. Disease relevance is evident across multiple contexts: the gene is deleted or epigenetically silenced by CpG methylation in approximately 10% of epithelial ovarian cancer cases 2, and truncating variants in FBXW12 have been identified as homozygous through loss of heterozygosity in neuroblastoma development 3. Additionally, a circular RNA derived from FBXW12 (circ-FBXW12) promotes diabetic nephropathy progression by sponging miR-31-5p 4. Clinically, FBXW12 variants contribute to interindividual variability in drug metabolism, specifically affecting losartan metabolism through CYP2C9 pathways 5, suggesting potential pharmacogenetic significance for personalized medicine applications.