Thus, the effect of the ATZ allele is twofold: (1) loss of functional α1AT in the bloodstream resulting in compromised connective tissue of the lung causing chronic emphysema; and (2) the accumulation of toxic aggregates in the hepatocyte ER, causing hepatitis, cirrhosis and an increased risk for hepatocellular carcinoma (HCC) (Valastyan and Lindquist, 2014). Here, SERPINA1 is linked to hepatocellular carcinoma.