Left ventricular noncompaction (LVNC) cardiomyopathy is a clinically and genetically heterogeneous disease that can be associated with substantial cardiovascular morbidity and mortality. A new study shows that mice with myocardial deletion of Mib1, which encodes a ubiquitin ligase in the Notch signaling pathway, have LVNC phenotypes and identifies MIB1 mutations in humans with LVNC (pages 193–201).