Gp130 receptor-mediated signaling promotes cardiomyocyte survival, induces hypertrophy, and modulates cardiac extracellular matrix and cardiac function.35 Cardiac-specific disruption of gp130 results in increased apoptosis of cardiomyocytes in response to ischemia or mechanical stress.1, 2 Inactivation of STAT3 resulting from the loss of gp130 is a crucial event in heart failure.35 In this regard, the gp130/STAT3 signaling pathway plays a key functional role for cardiac adaption and protection in response to various forms of stress leading to heart failure. The gene discussed is STAT3; the disease is heart failure.