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Lipolytic enzymes have been associated with the city of Marseille ever since the 1940s. At that time, the biochemists established tight links with the Marseille School of Chemistry for investiga- ting fat-splitting by enzymes, particularly the hydrolysis of triglycerides by lipases. Several important milestones on lipase research are associated with this long standing collaboration, from the molecular aspects of lipases to their physiological roles and their various medical and industrial applications. This story will be reviewed here through several highlights on pancreatic and gastric lipase research. Pancreatic lipase, which was for long the only lipase available for biochemical studies, still remains an attractive enzyme with the development of lipase inhibitors for obesity treatment. It is also used for enzyme replacement therapy in case of exocrine pancreatic insufficiency. Novel pancreatic lipase- related proteins have been identified and their physiological roles now extend from fat digestion to lipoprotein metabolism, lipid signaling and innate immunity.