A previous study confirmed that TGF-α is involved in ADM during the early stage of pancreatic carcinogenesis and local progression of PC,379–382 and it was demonstrated in 3D explant culture of primary pancreatic acinar cells that protein kinase D1 (PKD1), a downstream target of TGF-α and KRAS, is a mediator of ADM by activating the Notch signaling pathway.383 The combination of smad4 loss and tgfα overexpression was also shown to promote inflammation, ADM, fibrosis, and the formation and progression of PanIN lesions.384. The gene discussed is SMAD4; the disease is pachyonychia congenita.