In the current study, our analysis of genetic and pharmacological inactivation of HIPK2 in a mouse model of oncogenic KRAS-driven pancreatic cancer revealed that HIPK2 cooperates with the KRAS signaling for the development of ADM and PanIN lesions and the shape of desmoplastic reaction, and that HIPK2 inactivation can be explored as a preventive strategy. Here, KRAS is linked to pancreatic neoplasm.