SHCBP1 (SHC binding and spindle associated 1) is an adapter protein that binds the SH2 domain of Shc and regulates multiple signaling pathways critical for cellular proliferation and differentiation 1. Primary cellular functions include participation in FGF, MAPK/ERK, PI3K/AKT, NF-κB, TGF-β1/Smad, and β-catenin signaling, with roles in T cell development and cytokinesis 1. SHCBP1 localizes to the midbody and mitotic spindle, where it interacts with PLK1 to regulate mitosis 2. Mechanistically, receptor tyrosine kinase activation (HER2, EGF, EGFR) causes SHCBP1 detachment from Shc1 and Ser273 phosphorylation-dependent nuclear translocation 23. In the nucleus, SHCBP1 promotes mitotic progression through PLK1-MISP interaction or enhances cell migration via RACGAP1-RAC1 inhibition 23. SHCBP1 also suppresses ciliogenesis by preventing midbody remnant-centrosome proximity 4. Clinically, SHCBP1 is aberrantly expressed across multiple cancers including gastric, breast, lung, nasopharyngeal, and bladder carcinomas, correlating with poor prognosis 56. High SHCBP1 expression promotes tumor cell proliferation, invasion, metastasis, and apoptosis resistance while conferring trastuzumab and immune therapy resistance 27. SHCBP1 represents a promising diagnostic/prognostic biomarker and therapeutic target, with SHCBP1-PLK1 inhibition and MAPK pathway blockade showing therapeutic potential 5.