ABSTRACT Support is requested for a Keystone Symposia conference entitled Metabolic and Molecular Mechanisms of NAFLD/NASH, organized by Drs. James Trevaskis, Jacquelyn Maher and Quentin Anstee. The conference will be held in Banff, Alberta, Canada from March 19 - 23, 2023. Non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) represents the hepatic manifestation of the metabolic syndrome and is emerging as a key driver of morbidity and mortality, particularly when present in the context of severe liver fibrosis. The histological hallmarks of NASH including steatosis, lobular inflammation and hepatocyte ballooning are well-characterized; however, while it is widely recognized that NASH is a progressive disease, the pathogenic and molecular mechanisms that initiate and drive NASH remain largely unknown. Therefore, this conference was designed to bring together a broad group of scientific and clinical researchers to highlight and discuss the current evidence exploring the key biological processes involved in NASH and liver fibrosis. This conference program will cover topics such as insulin resistance, hepatocyte lipid management/lipotoxicity and inflammation in the context of steatosis and NASH. Furthermore, advances in our understanding of the molecular and genetic regulation of NAFLD/NASH and the progression to liver fibrosis will also be highlighted. Finally, as NASH is an unmet medical need, this program will integrate the earlier fundamental biology discussion with updates on clinical progress of therapeutic agents, and combinations of agents, for the treatment of NASH and liver fibrosis. Finally, this conference will be held jointly with Fibrosis Pathogenesis and Resolution: From Mechanisms to Therapies. The joint conference will focus on the key cellular drivers and mediators of fibrosis in organs beyond the liver and allows for cross-functional discussion and deeper understanding of pathobiology of fibrotic disease. Participants from both conferences will have the opportunity to network through shared sessions, mealtimes, and evening poster sessions.