Agents that trigger acute pancreatitis, such as alcohol and fatty acid ethyl esters, induce a sustained elevation of cytosolic Ca2+ due to Orai1-based CRAC channel opening, which leads to the activation of trypsin within endocytic vacuoles and mitochondrial Ca2+ overload, disrupting ATP production (Figure 3) [28,29]. This evidence concerns the gene ORAI1 and acute pancreatitis.