SUMMARY Advancing our understanding of human pancreatic diseases, especially pancreatitis and pancreatic cancer, requires the cooperative effort of a network of clinical centers of excellence and the regular meeting of thought leaders in the field. The course objectives for PancreasFest 2021: P.A.N.C.R.E.A.S. (Pain Autophagy Nutrition Cancer Rx Enzymes/ER Stress Acute & Chronic Pancreatitis Surgery) will enhance progress on meeting research priorities highlighted by the National Commission of Digestive Diseases. Specifically, we will 1) Critically review genetic and environmental risk factors associated with development of pancreatic diseases; 2) Critically review pancreatic pain and pain centralization; 3) Discuss strategies for translation of new scientific discoveries into clinical trials and practice, including needs analysis. The University of Pittsburgh has organized and hosted PancreasFest and its precursors since 1994. No other conference in the US focuses exclusively on fostering translational multi-center programs for pancreatic disorders. Attendees of past meetings uniformly praise PancreasFest for fostering collaborative research and emphasize the importance of having a small conference focused on pancreatic disorders. Multiple clinical working groups have emerged over the years through PancreasFest that focus on areas of NIDDK interest. Approximately 250+ medical professionals from varied medical disciplines register for PancreasFest each year, including physicians and scientists interested in the pancreas: gastroenterologists, surgeons, radiologists, pathologists, molecular biologists, pediatricians, geneticists, epidemiologists, statisticians, systems biologists, subspecialty medical professionals, and experts in biomarkers. We encourage attendance from junior faculty and trainees from the aforementioned disciplines to ensure that the next generation of pancreatic investigators interact directly with and learn from senior researchers in the field. Key staff from the NIDDK are invited to provide perspective and discuss priorities. PancreasFest is also attended by representatives from industry and patient-focused foundations, such as the National Pancreas Foundation. PancreasFest 2021 will be held at the Omni William Penn Hotel in downtown Pittsburgh, PA on July 21-23, 2021 and structured as a hybrid program. NIDDK-sponsored sessions will be part of PF21, which includes meetings from the International Study Group of Pediatric Pancreatitis In Search of a Cure (INSPPIRE) and the annual meeting of the Collaborative Alliance for Pancreatic Education and Research (CAPER), a nonprofit devoted to enhancing the career development of junior physician scientists in the field of pancreatology.