We suggest that FRG1 misregulation in a specific window of muscle differentiation may contribute to FSHD, although it cannot be considered the only molecular defect causing the FSHD phenotype: for example, the transcription of DUX4 recently observed in FSHD myoblasts [14,16] may contribute to the manifestation of FSHD. This evidence concerns the gene DUX4 and facioscapulohumeral muscular dystrophy.