Genetic risk in chronic pancreatitis: the misfolding-dependent pathwaySahin-Tóth, MiklósCurrent Opinion in Gastroenterology: September 2017 - Volume 33 - Issue 5 - p 390–395 doi: 10.1097/MOG.0000000000000380 PANCREAS: Edited by Rodger Liddle Abstract Author Information 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. Department of Molecular and Cell Biology, Center for Exocrine Disorders, Boston University Henry M. Goldman School of Dental Medicine, Boston, Massachusetts, USA Correspondence to Miklós Sahin-Tóth, Department of Molecular and Cell Biology, Center for Exocrine Disorders, Boston University Henry M. Goldman School of Dental Medicine, 72 East Concord Street, Evans-433, Boston, MA 02118, USA. Tel: +1 617 414 1070; fax: +1 617 414 1041; e-mail: firstname.lastname@example.org This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.