α-1-Antitrypsin Deficiency: Accumulation or Degradation of Mutant Variants within the Hepatic Endoplasmic Reticulum

Recent molecular and biochemical analyses of several alpha-1-antitrypsin variants suggest that the severe deficiency or complete absence of this protease inhibitor from serum results predominantly from the retention of mutant variants within the hepatic endoplasmic reticulum where they can accumulate or undergo intracellular degradation. Additional studies have demonstrated that the accumulation of the insoluble PiZ variant within this subcellular compartment acts as an etiologic agent for the development of liver disease in transgenic mice.