The S1P receptor, which is induced in cerebral microvessels early after I/R injury, potently regulates brain endothelium responses to ischemic and inflammatory injury.24 In addition, previous work in HUVEC cells has shown that knocking down Sphk1 can markedly impair their proliferation and migration.25 How endothelial Sphk1/S1P signaling impacts stroke prognosis via neovascularization and collateral establishment, however, remain uncertain. This evidence concerns the gene SPHK1 and stroke disorder.