In the present study, we used FtMt-overexpressing mice and a brain endothelial cell line, bEnd.3, as well as mouse models of middle cerebral artery occlusion (MCAO) stroke and oxygen–glucose deprivation followed by reoxygenation (OGD/R) to investigate the role and mechanisms of FtMt in BBB disruption during cerebral I/R. Here, FTMT is linked to stroke disorder.