Despite the limited number of mutations of neuroserpin (α1-antitrypsin) studied, Davis and colleagues show a direct correlation between severity of disease or magnitude of intraneuronal neuroserpin inclusions and predicted gradation of conformational instability of α1-antitrypsin mutants: G392E> H338R> S52R> S49P. Since homologous mutations cause α1-antitrypsin mutants to aggregate in the liver and produce cirrhosis, they conclude that intraneuronal protein aggregation is, in itself, or through the consequences that follow from it, a sufficient cause of neurodegenerative disease. The interpretation key I offer relates to α1-antitrypsin being a member of the serine protease inhibitors (SERPIN) and a low-affinity carrier of thyroid hormones. 2 Other SERPINs share this novel property: α1-chymotrypsin, antithrombin III, and corticosteroidbinding globulin (CBG). 2 Of interest, as Davis and colleagues cite, the homologous replacement of glycine 392 in antithrombin results in intracellular accumulation of the polymerised mutant protein. Also, transthyretin-related amyloidoses and transthyretin-related euthyroid hyperthyroxinaemia are mutually exclusive events. 3 Transthyretin is a non-SERPIN thyroid-hormone carrier of intermediate affinity, and several scattered mutations cause amyloidosis—a degenerative process leading to the extracellular aggregation