Hepatocellular carcinoma is one of the most common and deadliest cancers in the world due to limited treatment options and lack of knowledge of effective molecular targets. Thus, there is an urgent need to identify more effective therapeutic strategies to treat hepatocellular carcinoma. Emerging evidence has shown that canonical routes of glycogen metabolism are linked to hepatocellular carcinoma initiation and progression. However, the role of non-canonical routes of glycogen metabolism in hepatocellular carcinoma remains enigmatic. The objective of this proposal is to define how targeting non-canonical routes of glycogen metabolism modifies hepatocellular carcinoma in various mouse models. Completion of the proposed studies will greatly advance our understanding of glycogen metabolism in the context of hepatocellular carcinoma and potentially reveal a novel alternative approach to treat hepatocellular carcinoma, for which there are currently limited treatment options for.