SHCBP1 is a Shc SH2-domain binding protein involved in cell proliferation, growth, and differentiation. It acts as a key regulatory node in multiple signaling cascades including FGF, MAPK/ERK, PI3K/AKT, NF-κB, TGF-β1/Smad, and β-catenin pathways. Upon growth factor stimulation, SHCBP1 dissociates from the adapter protein Shc1, undergoes Ser273 phosphorylation, and translocates to the nucleus where it regulates mitotic processes and transcriptional activity. In normal cells, SHCBP1 participates in cytokinesis and T cell development. SHCBP1 is abnormally upregulated in multiple cancer types including nasopharyngeal carcinoma, gastric cancer, bladder cancer, breast cancer, and ovarian cancer, where it promotes proliferation, invasion, migration, and metastasis 12. In HER2-positive gastric cancer, the HER2-SHCBP1-PLK1 axis drives trastuzumab resistance, and theaflavine-3,3'-digallate has been identified as an inhibitor of SHCBP1-PLK1 interaction with potential to restore trastuzumab sensitivity 3. In ductal carcinomas, SHCBP1 suppresses ciliogenesis, and its deletion restores primary cilia formation and inhibits tumor progression 4. In ovarian cancer, SHCBP1 confers cisplatin resistance through AKT/mTOR pathway activation, and combination therapy with cisplatin and SHCBP1 inhibition shows promise 5. SHCBP1 expression correlates with clinicopathological features and poor prognosis, positioning it as both a diagnostic biomarker and therapeutic target across multiple malignancies.