Defects of growth inhibitory pathways have an important role in disorders of cell growth and differentiation. The discovery of a mutation in one of the principle components of the transforming growth factor β (TGFβ) receptor system which is linked to a DNA repair defect(1) represents one possible mechanism of escape from negative regulatory influences acting upon cells. TGFβ is a pre‐eminent negative growth factor and this article discusses (1) the role of TGFβ in maintaining epithelial homeostasis; (2) how breakdown of (...) inhibitory pathways can promote neoplastic development; (3) the significance of a receptor defect in a negative signalling pathway; and (4) the potential therapeutic sequelae resulting from restoration of cellular responsiveness to TGFβ. (shrink)