Alpha-1-proteinase inhibitor (A1PI) (A1PI)

Alpha-1-proteinase inhibitor (A1PI), also known as alpha-1-antitrypsin (AAT), is a major circulating serine protease inhibitor (serpin) primarily synthesized in the liver (UniProt P01009). Its primary biological role is to protect delicate lung tissues from degradation by neutrophil elastase, an enzyme released by white blood cells during inflammation (StatPearls, Alpha 1 Antitrypsin Deficiency). In individuals with alpha-1 antitrypsin deficiency (AATD), low levels of functional A1PI lead to an imbalance between proteases and antiproteases, resulting in progressive lung destruction and emphysema (StatPearls, Alpha 1 Antitrypsin Deficiency). Additionally, the accumulation of misfolded A1PI proteins in hepatocytes can cause liver damage and cirrhosis (UniProt P01009). Therapeutic intervention typically involves augmentation therapy, where purified A1PI from human plasma is administered intravenously to restore protective levels in the lungs (FDA, Prolastin-C). Current research also explores gene therapies and small molecules to address the underlying genetic causes and protein misfolding associated with the deficiency (StatPearls, Alpha 1 Antitrypsin Deficiency). Beyond its role in the lungs, A1PI exhibits anti-inflammatory and immunomodulatory properties that may be beneficial in other conditions like type 1 diabetes or graft-versus-host disease (UniProt P01009).

Other names

Alpha-1-antitrypsinA1ATSerpin A1Alpha-1-antiproteinaseProtease inhibitorPI

Augmentation therapy; exogenous administration of purified A1PI restores the protease-antiprotease balance and inhibits neutrophil elastase to prevent lung tissue degradation (StatPearls, Alpha 1 Antitrypsin Deficiency; FDA, Prolastin-C).