The invention provides methods for efficient recombinant expression, refolding, and purification of Beta-site APP cleaving enzyme (BACE) polypeptides. In various aspects, the method includes the steps of expressing a recombinant construct in bacteria, dissolving inclusion bodies with a denaturant at high pH in the presence of a reducing agent, diluting the solubilized BACE polypeptide in an aqueous solution at a temperature of about 1.degree. C. to 15.degree. C., and incubating the diluted sample at a temperature of about 4.degree. C. to 15.degree. C. until the recombinant BACE polypeptide folds into an active enzyme.