Given the increasing popularity of the double-transgenic ACTA1-MCM/FLExDUX4 mouse model for studying FSHD and its important similarities to patient phenotypes (i.e., disease-relevant low and stochastic DUX4 expression, progressive muscle wasting, reduction in muscle strength, and elevation in muscle fibrosis) [21,22], we sought to confirm berberine’s efficacy in inhibiting DUX4 in these transgenic mice. This evidence concerns the gene DUX4 and facioscapulohumeral muscular dystrophy.