RBFOX1 and facioscapulohumeral muscular dystrophy: However, in an FSHD mouse model and in FSHD patients, the down-regulated expression of RBFOX1 protein due to decreased mRNA stability causes defective splicing of calpain 3 pre-mRNA, which generates a protein isoform that disrupts the balance between global protein synthesis and degradation in adult muscle (Pistoni et al., 2013).