Given the similarity of the conformational features associated with each AAT variant between the intracellular and extracellular space, we use the measured levels of intracellular polymer, secreted monomer and the NE inhibitory activity from Huh7.5null cells henceforth to understand how, on a residue-by-residue basis, the folding of AAT is coupled to function to drive different disease states found in the AATD population. This evidence concerns the gene SERPINA1 and alpha 1-antitrypsin deficiency.