DUX4 induces changes in the expression of hundreds of genes that impact dozens of highly interconnected pathways (Geng et al., 2012; Block et al., 2013; Young et al., 2013; Banerji et al., 2015; Feng et al., 2015; Homma et al., 2015; Dmitriev et al., 2016; Shadle et al., 2017), making a cause-and-effect relationship between dysregulated gene expression and FSHD pathology difficult to discern. Here, DUX4 is linked to facioscapulohumeral muscular dystrophy.