CTRL (chymotrypsin-like protease) is a serine protease belonging to the chymotrypsin family that functions as a pancreatic digestive enzyme with protective roles against pancreatitis 1. The protein exhibits serine-type endopeptidase activity and can cleave trypsinogens, leading to trypsin suppression and degradation 2. Mechanistically, CTRL demonstrates proteolytic activity against trypsinogen substrates, effectively reducing harmful trypsin activation within the pancreas 2. However, CTRL represents a low-abundance isoform among pancreatic chymotrypsins, as evidenced by minimal reduction in total chymotrypsinogen content in CTRL-deficient mice 2. Disease relevance studies show mixed findings regarding CTRL's role in chr16 pancreatitis. While several CTRL variants have been identified in pancreatitis patients, including variants with reduced or abolished proteolytic activity and impaired secretion, these loss-of-function variants were not significantly more common in patients compared to controls 1. In experimental models, CTRL-deficient mice showed altered intrapancreatic protease activation patterns but no significant difference in pancreatitis severity 2. Clinically, these findings suggest that while CTRL contributes to pancreatic protease regulation, it is unlikely to play a major role in chr16 pancreatitis development, contrasting with other chymotrypsin family members 1.