KRAS and neoplasm: Here, we present evidence that in the initial course of PDAC development AGR2 can be induced in pancreatic cells as a response to ER stress and/or oncogenic KRAS even before visible neoplasia; we reveal a critical role for AGR2 in the formation of KRAS-driven pre-neoplastic lesions, and we demonstrate that ER stress is associated with the development of a pro-inflammatory microenvironment.