Since the first reports of disease-causing CCM1 variants in familial CCM cases (Laberge-le Couteulx et al., 1999; Sahoo et al., 1999), we have learned a lot about CCM pathogenesis and the endothelial dysfunction in cavernous lesions (Maddaluno et al., 2013; Cuttano et al., 2016; Zhou et al., 2016; Detter et al., 2018; Malinverno et al., 2019; Hong et al., 2020; Ren et al., 2021). This evidence concerns the gene KRIT1 and cerebral cavernous malformation.