Thus, it is possibly that the recently reported causative relationship between the hyperexpression of two normally cytoprotective transcription factors, such as KLF2 and KLF4, and CCM pathogenesis (Cuttano et al., 2016, Zhou et al., 2016) could be connected to autophagic defects and oxidative stress events associated with loss-of-function of CCM proteins. This evidence concerns the gene KLF4 and cerebral cavernous malformation.