In summary, our study demonstrates that XIAP is a key mediator of cell death in acute pancreatitis through its effects on caspases, RIP1 and NF-κB. Lack of XIAP in acute pancreatitis decreases the activation of NF-κB, increases caspases activities and RIP1 degradation, leading to less inflammatory response, increased apoptosis and decreased necrosis in acute pancreatitis, resulting in reduced severity of acute pancreatitis. Here, NFKB1 is linked to acute pancreatitis.