Point mutations cause members of the serine protease inhibitor (serpin) superfamily to
undergo a novel conformational transition, forming ordered polymers. These polymers
characterize a group of diseases termed the serpinopathies. The formation of polymers
underlies the retention of α1-antitrypsin within hepatocytes and of neuroserpin within
neurons to cause cirrhosis and dementia, respectively. Point mutations of antithrombin, C1
inhibitor, α1-antichymotrypsin, and heparin cofactor II cause a similar conformational …