A recent study by Lassche et al. (2020) hypothesized that muscle weakness in FSHD is not caused by alterations in sarcomeric contractility, or excitation–contraction coupling (Vandebrouck et al. 2002), but is due to DUX4-induced toxicity and consequential loss of muscle fibers or to an unknown impaired metabolic cause. The gene discussed is DUX4; the disease is facioscapulohumeral muscular dystrophy.