Although AATD-associated liver disease results from accumulation of misfolded, polymerized Z-AAT within hepatocytes and associated gain-of-function toxicity,6 AATD-associated emphysema has been attributed primarily to loss of antiprotease function, unopposed neutrophil elastase activity, and resultant pulmonary parenchymal destruction. Here, ELANE is linked to alpha 1-antitrypsin deficiency.