Metabolic remodeling, marked by maladaptive shifts in substrate use and energy production, is a hallmark of pathologic cardiac hypertrophy. Yet the mechanisms linking stress signaling to impaired myocardial glucose oxidation remain incompletely defined. Sam68 (Src-associated in mitosis, 68 kDa; also known as KHDRBS1 [KH domain-containing, RNA-binding, signal transduction-associated protein 1]), a STAR (signal transduction and activation of RNA) family RNA-binding protein, has not previously been implicated in cardiac metabolic control.