Abstract: Provided are methods for producing biologically active mutant recombinant plasminogen polypeptides with desired pharmaceutical properties. The refolded polypeptides may be treated with a plasminogen activator, such as tPA, urokinase, or streptokinase to generate biologically active mutant plasmin polypeptide for pharmaceutical use. Methods are also provided to producing biologically active fusion recombinant mutant plasminogen/plasmin polypeptides that can cross the BBB through receptor mediated transcytosis. The fusion partner may carry the mutant plasminogen/plasmin polypeptides into the brain for increased therapeutic efficiency.