Our main findings were: (1) LVO-induced AIS patient data strongly correlated collateral status with plasma FSAP levels, (2) FSAP levels were also able to independently predict clinical outcome at 3-month follow-ups, (3) FSAP could induce endothelium apoptosis, and weaken cell viability, proliferation, migration and tube formation of PBMECs, (4) FSAP blockade increased cerebral blood flow, improved BBB integrity, promoted collateral formation, and resulted in better neurological function in experimental stroke models, finally (5) FSAP modulated endothelium function via the Wnt5a pathway. This evidence concerns the gene WNT5A and stroke disorder.