Ubc13-mediated ubiquitination of AKT is required for activation of the insulin signaling pathway. GPS2 regulates insulin signaling by inhibiting AKT ubiquitination and activation. Adipo-specific deletion of GPS2 results in increased adiposity and altered lipid flux in the adipocytes. GPS2-AKO mice have higher levels of circulating adiponectin and are insulin sensitive despite being obese.