As transient and pulsatile expression of DUX4 is sufficient to induce pathology and cell death (Rickard et al., 2015), it is critical that we understand the cellular events and pathways set in motion by DUX4 that lead to eventual cell death, in order to develop effective therapeutics for FSHD. This evidence concerns the gene DUX4 and facioscapulohumeral muscular dystrophy.