Here we examine the relationship of GDF15 with heart failure and its role in cardiac cachexia, utilizing mice that lack catalytically active PPP1R15A.16 In our initial studies examining the role of PPP1R15A in different models of heart failure using bone marrow transfer protocols involving whole body irradiation, we serendipitously identified that PPP1R15A is critical in the prevention of irradiation-induced left ventricular heart failure and associated cardiac cachexia. This evidence concerns the gene GDF15 and heart failure.