A specific MEK5 inhibitor BIX-02189 (Tatake et al., 2008) significantly decreases pERK5 and KLF4 expression, inhibits Bmp6 upregulation and EndMT in CCM1 deficient ECs (Cuttano et al., 2016), indicating that inhibitors of the MEKK3-MEK5-ERK5-MEF2 axis might be useful for suppressing BMP signaling and EndMT in the pathogenesis of CCM. This evidence concerns the gene KLF4 and cerebral cavernous malformation.