Because CCM‐associated cardiovascular defects in mouse and zebrafish models have been linked to an activation of the MEKK3‐MEK5‐ERK5 signaling pathway (Zhou et al, 2015; Cuttano et al, 2016) and elevated levels of KLF2 (Renz et al, 2015; Zhou et al, 2015, 2016), we next tested the molecular effects of IR3mo treatment on these phenotypes in different CCM models. This evidence concerns the gene MAP2K5 and cerebral cavernous malformation.