FIGURE 3.

Schematic mechanism underlying mutations associated with pancreatitis. The PRSS1 mutation (blue arrow) leads to a gain-of-function with an increased conversion of trypsinogen to trypsin and increased trypsin stability. The SPINK1 and CTRC mutations (red line) lead to an imbalance of proteases and antiproteases with the respective losses of first and second-line defences against the activation of trypsinogen and the enzymatic cascade that leads to autodigestion and pancreatitis. Mutations in CPA1 generate misfolded proteins in the endoplasmic reticulum (ER), leading to ER stress and the development of pancreatitis.