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The past decade has seen rapid advances in our understanding of the fibrogenic process in the pancreas mainly due to the elucidation of the biology of the cells that are critical to this process. However, it is also becoming increasingly clear that PSCs do not merely exist to regulate ECM turnover in health and disease, but may also have other important roles in the normal pancreas as immune cells and/or progenitor cells. In vitro and in vivo experimental studies have provided encouraging results in terms of developing therapeutic strategies to target PSCs in chronic pancreatitis and pancreatic cancer. The challenge that remains is to translate these findings to the clinical situation so as to improve the outcome for patients afflicted with these diseases.