Cerebral cavernous malformations (CCMs) are congenital vascular anomalies of the CNS, which can result in a variety of neurological disabilities, including hemorrhagic stroke and seizures. To date, there is not any known homologous structure of CCM2 reported. CCM2 contains two independent domains. The N-terminus of CCM2 is a phosphotyrosine binding (PTB) domain, and the C-terminus of CCM2 is called the Karet domains, which is required for death signaling. Here we report the crystal structures of CCM2(MGC4607, OSM) C-domain, CCM2 -Ct(residues 290-444) at 2.7Å. The overall structure of CCM2-Ct consists of six helices (α1-α6), all the six helices fold into a compact six-helix bundle, in which the tandem α1-α5 helices make up the major fragment and the sole α6 constitutes the minor fragment. A number of hydrophobic residues in the four helices, form a hydrophobic core to stabilize the structure. On the outside surface of each helix-hairpin, there is a preformed cleft. The last two helices, α5 and α6, are wedged into the clefts. The long flexible loop (residues 378-423) linking the sole helix and the α1-α5 degrades spontaneously. On the basis of the structure’s feature, we align the C-domain to other protein complex in the PDB. We put up this hypothesis that CCM2 could bind to its target proteins by exchanging the helix as an important adaptor protein.