In this context, our findings that KRIT1 plays an expression level-dependent role in the regulation of ROS homeostasis, as well as a protective role against oxidative DNA damage, raise the hypothesis that a reduction of KRIT1 levels in heterozygous CCM mutation carriers may facilitate DNA damage due to increased ROS levels, leading to the loss of the second KRIT1 allele (second hit) and resulting in the local formation of CCM lesions. This evidence concerns the gene KRIT1 and cerebral cavernous malformation.