How DUX4 expression causes the muscle degenerative phenotypes associated with FSHD is still an active area of investigation; however, substantial evidence suggests that activation of the DUX4 transcriptional program in skeletal muscles leads to phenotypes including oxidative stress, DNA damage, loss of proteostasis, and inflammation, which culminate in myofiber death (Bosnakovski et al., 2017; Dmitriev et al., 2016; Homma et al., 2015; Rickard et al., 2015; Shadle et al., 2017). The gene discussed is DUX4; the disease is facioscapulohumeral muscular dystrophy.