Advances in the understanding of DUX4 regulation, the consequences of its activation and the pathophysiological mechanisms leading to muscle wasting in FSHD, along with the development of more accurate and multi-systemic disease models, the surge of interventional strategies, as well as the validation of more sensitive outcome measures and the expansion of a trial-ready clinical network reflect a promising landscape for the development of therapies for FSHD. Here, DUX4 is linked to facioscapulohumeral muscular dystrophy.