FBXO15 (F-box protein 15) functions as a substrate-recognition component of SCF-type E3 ubiquitin ligase complexes, directing target proteins for proteasomal degradation 1. The protein localizes to the cytosol and mediates ubiquitin-dependent protein catabolism through its interaction with ubiquitin-conjugating enzymes, particularly UBE2R1 12. Mechanistically, FBXO15 recognizes phosphorylated substrates through phosphodegron motifs. In mitochondrial homeostasis, FBXO15 cooperates with PINK1 kinase to target cardiolipin synthase 1 (CLS1) for degradation; bacterial pathogens exploit this pathway to impair mitochondrial function during acute lung injury 3. In multidrug resistance, FBXO15 directs P-glycoprotein degradation via UBE2R1-mediated ubiquitination, with FBXO15 knockdown increasing drug resistance 12. Clinically, FBXO15 variants associate with multiple pathologies. Genomic analysis identified an intergenic variant near FBXO15 linked to tuberculosis severity and host-pathogen genetic interactions 4. Hemizygous deletions involving FBXO15 on chromosome 18 correlate with autism-like behaviors 5. FBXO15 also associates with thyroid function variation, showing gender-specific effects on free thyroxine levels 6, and represents a candidate locus in degenerative cervical myelopathy 7. Additionally, dysregulated FBXO15 expression appears involved in retinoblastoma progression through ubiquitination-related miRNA pathways 8.