Here, we demonstrated the potential link between NGBR loss and CCM pathogenesis by rescuing CCM1/2 expression in mice with inducible EC-specific knockout of Ngbr and elucidated the molecular mechanism by which NGBR regulates the transcription of CCM1/2 genes through HBO1-mediated histone acetylation. Here, KAT7 is linked to cerebral cavernous malformation.