Treatment of DMD requires production of functional dystrophin at levels far below those found in healthy individuals and in only a fraction of myofibers, whereas treatment of FSHD may well require much higher doses to achieve DUX4 repression, which will likely be required in a majority of myofibers, since every muscle nucleus is poised to express DUX4 at any given time. Here, DUX4 is linked to facioscapulohumeral muscular dystrophy.