In the case of Rap1 activation by LPS or other extracellular stimuli, the Rap1 signal is transduced through distinct effector(s) like RIAM (Rap1–GTP-interacting adapter molecule), KRIT-1/CCM (Krev-1/Rap1 interaction trapped 1/cerebral cavernous malformation) and AF-6/Cno (ALL1-fused gene from chromosome 6 protein) proteins, which can assemble adhesion complexes that are distributed uniformly [28]. This evidence concerns the gene AFDN and famililal cerebral cavernous malformations.