Alpha-1 antitrypsin (AAT) deficiency is one of the most common hereditary conditions affecting the lungs and liver, with an estimated prevalence of 1 in 2,000-5,000 individuals of European descent. It is an autosomal codominant disorder caused by mutations in the SERPINA1 gene on chromosome 14, which encodes alpha-1 antitrypsin, a serine protease inhibitor (serpin) primarily produced by hepatocytes. AAT deficiency leads to two distinct organ pathologies through two different mechanisms: destructive lung disease from unopposed protease activity and liver disease from toxic accumulation of misfolded AAT protein within hepatocytes. Alpha-1 antitrypsin is the most abundant circulating serine protease inhibitor in human plasma, with normal serum levels of 100-220 mg/dL. Its primary physiological function is to protect the lower respiratory tract from destruction by neutrophil elastase, a powerful serine protease released by activated neutrophils during their normal antimicrobial function. Neutrophil elastase is capable of degrading virtually all components of the extracellular matrix, including elastin (the structural protein that gives the lung its elastic recoil), collagen, and proteoglycans. Under normal circumstances, AAT rapidly binds to and inactivates neutrophil elastase through a suicide-substrate...