Idiopathic pulmonary fibrosis (IPF) is a progressive disease of the lung parenchyma, causing significant morbidity and mortality 1, 2. The therapeutic options in IPF are limited to only two recently approved drugs, pirfenidone and nintedanib, which have been shown to slow progression but are not able to stop or reverse the disease 3, 4. Better pathophysiological knowledge is needed to develop new therapeutic strategies in IPF. The current understanding of the disease is that fibroblastic foci, characterised by accumulation of myofibroblasts and overlying “activated” epithelium, represent “hot zones” of the disease and drivers of abnormal extracellular matrix (ECM) accumulation 5. Transforming growth factor (TGF)-β1 is a key cytokine involved in the process of fibrogenesis. TGF-β1 causes myofibroblast proliferation and differentiation and increases the synthesis of collagen, fibronectin and many other ECM components 5. The TGF-β1 signalling pathways are complex and occur essentially through serine/threonine kinase receptors, TGF-β receptors type I and II (TGF-βRI and TGF-βRII). TGF-βRII is constitutively active and activates TGF-βRI via phosphorylation upon ligand binding 6. The cytoplasmic proteins Smad2 and Smad3 predominantly mediate signals from activated TGF-β1 receptors. Activation of Smad2 and Smad3 via phosphorylation makes them bind to Smad4, promoting translocation to the nucleus where numerous TGF-β1-responsive genes are activated. TGF-β1 pathways are undoubtedly very promising but also challenging targets to treat fibrosis and in particular IPF.