The invention discloses a novel application of fibrinogen-420 and its active domain (alpha EC domain), and a separate alpha EC domain protein has the same or similar function with fibrinogen-420. Fibrinogen-420 and its active domain can be widely used in inhibiting protein aggregation, helping protein refolding, drugs which can prevent and/or treat protein conformation disease, detecting denatured protein in quality control and protect protein from denaturation.