The recent article from Gómez‐del Arco et al (2016) in Cell Metabolism reveals the essential role of chromodomain‐helicase‐DNA‐binding protein 4 (CHD4) in the control of alternative gene expression in cell types that share seemingly redundant, yet distinct, biological properties, such as the contractile activities of striated cardiac or skeletal muscles. An altered expression of genes for alternative sarcomeric and metabolic programs occurred upon genetic inactivation of Chd4 in skeletal or cardiac cells, leading to formation of “hybrid” striated muscles and pathological outcomes.