The serpinopathies result from point mutations in members of the serine protease inhibitor or
serpin superfamily. They are characterized by the formation of ordered polymers that are
retained within the cell of synthesis. This causes disease by a “toxic gain of function” from
the accumulated protein and a “loss of function” as a result of the deficiency of inhibitors that
control important proteolytic cascades. The serpinopathies are exemplified by the Z
(Glu342Lys) mutant of α 1-antitrypsin that results in the retention of ordered polymers within …