Despite the knowledge of CCM complex involvement, the severity and natural course of the disease are highly variable, even in patients carrying the same genetic mutations [1–3], suggesting the existence of others genetic/epigenetic factors and/or environmental disease modifiers, some of which involving inflammatory mediators, that affect disease outcomes, probably by activating the MEKK–KLF2/4 pathway [8, 9]. The gene discussed is KLF2; the disease is cerebral cavernous malformation.