SERPINA1 and pulmonary emphysema: The main physiological role for A1AT is protection of the extracellular matrix of the lung from proteolytic damage arising from the release of proteases during an inflammatory response, primarily neutrophil elastase but with some reactivity against proteinase 3 and cathepsin G. When A1AT forms aggregates of inactive polymers, these molecules deposit within the liver, causing cirrhosis, and the lack of circulating A1AT leads to proteolytic dysregulation within the lung, predisposing to the development of emphysema.