Purpose of review: Genetic risk in chronic pancreatitis is partly due to mutations that cause misfolding of digestive enzymes and elicit endoplasmic reticulum stress. This review examines recent developments in this concept.
Recent findings: The best characterized misfolding variants in the highly expressed digestive proteases cationic trypsinogen (PRSS1) and carboxypeptidase A1 (CPA1) are strong, causative risk factors for chronic pancreatitis and may be associated with autosomal dominant hereditary pancreatitis.
Summary: Properties of misfolding digestive enzyme mutants indicate that endoplasmic reticulum stress is a highly relevant pathological mechanism and a potential therapeutic target in chronic pancreatitis.