Interestingly, our biochemical and structural data indicates a different mode of modulation of SnoN compared to that of Ski, which may reflect differences in the biological function of these modulators in TGF-β signaling – an insight that opens up new avenues for modulator-specific therapeutic intervention in their respective roles in metastatic cancers. The gene discussed is TGFB1; the disease is metastatic malignant neoplasm.