We propose a central involvement of TGF-β signaling in IPF, alongside other mediators such as TP53, SMAD3, BMP7, MRTFB, TEAD, GLIS1 and APOE, which are linked to senescence, myofibroblast activation and differentiation, Notch and Wnt signaling, apoptosis and cell migration. The gene discussed is APOE; the disease is idiopathic pulmonary fibrosis.