Given that SPDEF has been linked to an indolent, pyloric-like phenotype in IPMN (12), our findings raise the possibility that NRF2 loss promotes IPMN formation by derepressing SPDEF activity, shifting pancreatic epithelial fate toward a mucinous differentiation program. This evidence concerns the gene SPDEF and pancreatic intraductal papillary-mucinous neoplasm.