FBXW10 is an F-box and WD repeat domain protein functioning as a substrate-recognition component of SCF-type E3 ubiquitin ligase complexes 1. It mediates ubiquitination and proteasomal degradation of target proteins through K63-linked polyubiquitination mechanisms 1. In hepatocellular carcinoma (HCC), FBXW10 promotes K63-linked polyubiquitination of annexin A2 (ANXA2), enabling S6K1-mediated phosphorylation and ANXA2 membrane translocation, which activates KRAS and the MEK/ERK proliferation pathway 1. FBXW10 also demonstrates male-biased oncogenic function, with significantly higher expression and poor prognostic correlation in male HCC patients 2. In colorectal cancer, FBXW10 ubiquitinates and degrades LATS2 tumor suppressor, promoting angiogenesis and liver metastasis 3. FBXW10 expression is upregulated in multiple cancers including thyroid carcinoma, where zinc finger protein 169 (ZNF169) transcriptionally activates FBXW10 4. Conversely, protein O-GlcNAcylation negatively regulates FBXW10 expression at both transcriptional and translational levels 5. In clear cell renal cell carcinoma, abnormal FBXW10 hypermethylation correlates with higher tumor grades and poor prognosis 6. These findings establish FBXW10-mediated ubiquitination as a critical oncogenic driver across multiple cancer types with potential therapeutic targeting implications.