Pancreatic acinar cells are polarized epithelial cells that store enzymes required for digestion as inactive zymogens, tightly packed at the cell apex. Stimulation of acinar cells causes the zymogen granules to fuse with the apical membrane, and the cells undergo exocytosis to release proteases into the intestinal lumen. Autophagy maintains homeostasis of pancreatic acini. Syntaxin 2 (STX2), an abundant SNARE protein in pancreatic acini, has been reported to mediate apical exocytosis. Using human pancreatic tissues and STX2-knockout mice, we investigated the functions of STX2 in zymogen granule-mediated exocytosis and autophagy.