Cerebral cavernous malformations 2 protein (CCM2)

Cerebral cavernous malformations 2 protein (CCM2), also known as malcavernin, is a cytosolic scaffold/adapter protein essential for maintaining endothelial cell–cell junctions, vascular permeability, and overall neurovascular integrity[1][4][5][6][7]. CCM2 forms part of a multiprotein complex with CCM1/KRIT1 and CCM3/PDCD10, acting as a central organizing hub that coordinates signal transduction between critical pathways, including the stress-activated p38 MAPK pathway (by scaffolding MEKK3 and RAC1), and the RhoA-dependent regulation of the actin cytoskeleton[1][4][5][6][7]. Loss-of-function mutations in CCM2 disrupt these signals, leading to weakened vessel walls, increased vascular permeability, and the formation of cerebral cavernous malformations—clusters of fragile, leaky blood vessels in the brain and spinal cord associated with headaches, seizures, and risk of hemorrhage[6][7]. CCM2 has no known intrinsic enzymatic activity but interacts with diverse protein partners, and its PTB and harmonin homology domains mediate these scaffolding functions[1][3][4][5]. While currently not the direct target of approved pharmacotherapies, CCM2 is of translational interest for vascular diseases, neurovascular lesions, and molecular diagnostics.

Other names

MalcaverninOsmosensing scaffold for MEKK3C7orf22CCM2 scaffolding proteinMGC4607OSMPP10187Cerebral cavernous malformation 2 protein