GNAS mutations contribute to pancreatic intraductal papillary mucinous neoplasm (IPMN) formation, but underlying mechanisms—and cell type specificity therein—have yet to be delineated. In their study on page 440, Desai and colleagues interrogated cell type-specific GNAS^R201C signaling in human stem cell-derived pancreatic ductal and acinar organoids containing doxycycline-inducible GNAS^R201C. The authors found that GNAS^R201C induced IPMN-like growth and cell proliferation more readily in ductal than acinar organoids, and that those phenotypes were uniquely protein kinase A (PKA)-independent in ductal organoids. The cover features a confocal image of a GNAS^R201C-expressing pancreatic ductal organoid section in the presence of a pharmacologic PKA inhibitor, where proliferating cells are labeled with Edu (white) and DAPI-stained nuclei fluoresce purple. This study is also Highlighted on page 421.