In this disease, destabilized AAT variants (e.g., PIZZ) can lead to both gain of toxic function pathology through intra-ER retention causing liver pathology and loss-of-function pathology associated with poorly functional secreted AAT leading to chronic obstructive pulmonary disease in the lung (Lomas and Mahadeva, 2002; Silverman and Sandhaus, 2009). The gene discussed is SERPINA1; the disease is chronic obstructive pulmonary disease.