**4.2 Inappropriate protease activation**

Pancreatic acinar cells secrete proteases as precursor enzymes, which are then activated by the serine protease in the duodenum [25]. Trypsin, the precursor of the major protease trypsinogen, starts the activation cascade of many other proteases, and itself in the duodenum (autoactivation). The natural inhibitors of the intrapancreatic activation are the SPINK1, trypsinogen degradation by CTRC and cathepsin L. Most genetic mutations associated with CP are trypsin dependent. Premature intrapancreatic activation or inappropriate inhibition of the trypsinogen can lead to pathologic event resulting in CP [26].
