Inactivating mutations in genes encoding components of the TGFβ signalling pathway feature as common events in CRC and can occur both at the cell-receptor level (TGFBR2 frameshift mutations in microsatellite-unstable/mismatch repair-deficient CRC) and the transcriptional-effector level (mutations in SMAD4—the common denominator of canonical TGFβ signalling—in microsatellite stable CRC)10,11. The gene discussed is TGFBR2; the disease is colorectal carcinoma.