Taken together, our data demonstrated that loss of Prdm3 not only increased the severity of cerulein-induced pancreatitis, but also accelerated cellular atypia and tumorigenic potential in the pancreas, as Prdm3-deficient mice undergo robust formation of precursor lesions in the presence of oncogenic Kras. We uncovered a previously unappreciated role for Prdm3 as a suppressor of both pancreatitis and pancreatic tumorigenesis presumably through regulating inflammatory and Hif-1 signaling pathways in the pancreatic acinar cells. The gene discussed is MECOM; the disease is pancreatitis.