FBXW9 is an F-box protein that functions as a substrate-recognition component of SCF-type E3 ubiquitin ligase complexes, mediating proteasome-dependent protein degradation 1. The gene is regulated downstream of IGFBP5-ROR1/HER2-CREB signaling in glioblastoma stem cells, where it promotes invasion and tumorigenesis 2. FBXW9 is upregulated across multiple cancer types, particularly breast cancer, and shows prognostic significance 1. It likely targets tumor suppressors, with TP53 identified as a potential substrate hub; FBXW9 knockdown increases p21 expression and inhibits cancer cell proliferation and cycle progression 1. Expression of FBXW9 correlates with poor prognosis in breast cancer patients receiving anti-PD1 immunotherapy and is associated with cancer stem cell properties and MYC-related gene activities 1. Additionally, germline FBXW9 variants have been identified in familial and early-onset multiple myeloma cases, suggesting potential hereditary disease susceptibility 3. The gene demonstrates stable, low baseline expression across hematological malignancies, making it suitable as a reference gene for qPCR-based diagnostic assays 4.