The exact mechanism by which cerebral cavernous malformations arise is still subject to debate, with deregulation of several signalling pathways such as RHO (Richardson et al., 2013; Stockton et al., 2010; Borikova et al., 2010; Whitehead et al., 2009), TGFβ (Maddaluno et al., 2013), β-catenin (Bravi et al., 2015) and MEKK3–KLF2 or MEKK3–KLF4 (Cuttano et al., 2016; Zhou et al., 2016; Renz et al., 2015) having been demonstrated to be involved in development and progression of the disease. This evidence concerns the gene MAP3K3 and cerebral cavernous malformation.