To dissect potential interplaying roles and underlying mechanisms of aberrant RNF43 and KRAS in IPMN initiation and malignant transformation, we simulated human IPMN and PDAC in mice by establishing a pancreatic KrasG12D and Rnf43 deficient preclinical model. Here, RNF43 is linked to pancreatic intraductal papillary-mucinous neoplasm.