Xirp2, also known as cardiomyopathy-associated protein 3 (Cmya3), was first identified in cardiac tissue of humans with cardiomyopathy (Duka et al., 2006) and has been shown to be upregulated in other forms of cardiac disease, including pressure-overload hypertrophy (Wang Q. et al., 2012) and during angiotensin-II remodeling (Duka et al., 2006; McCalmon et al., 2010), yet it is decreased in heart failure and idiopathic dilated cardiomyopathy (Wang et al., 2014). Here, XIRP2 is linked to heart failure.