One of the most important recent advances in our understanding of the basic mechanisms of genetic cardiac disease has been the central role played by mutations in structural proteins. Nearly 2 decades ago Geisterfer-Lowrance et al.(1) published the first linkage of a mutation in the beta-MyHC gene to hypertrophic cardiomyopathy (HCM). Since that seminal finding, mutations in a broad array of proteins that contribute to the structural and functional integrity of components of the cardiac sarcomere, myocellular cytoskeleton, and the sarcolemma have been definitively linked to a vast range of clinical cardiomyopathies (2). Sarcomeric protein mutations represent a particularly intriguing subset of the genetic cardiomyopathies in that independent mutations within the same gene and often within the same functional domain can cause widely divergent, clinically relevant patterns of pathogenic ventricular remodeling.