The serpin family of proteins consists of over 1500 members, all with a highly conserved native structure that is metastable (1). Serpins use this metastability to control the activity of proteases, via a specific inhibitory process. The serpin binds to its target protease through specific residues within the reactive centre loop, the protease cleaves the loop and results in a large conformational change causing the protease to become distorted and catalytically inactive whilst the serpin becomes much more stable (1, 2, 3). The metastable nature of AAT is therefore required to facilitate the rapid and gross conformational changes required for its inhibitory function (2, 3). Several disease-causing mutants of AAT have been identified, the most common of them being the Z-variant (4). The Z-variant has an increased propensity to polymerize in the endoplasmic reticulum of hepatocytes leading to cell death and liver damage (4). During the past fifteen years, many groups have unsuccessfully screened a number of serpins and a vast range of solution conditions to identify a combination of serpin and conditions that will enable the folding reaction of a serpin to be characterized. We have now taken an alternative approach and designed a synthetic “model” serpin that folds reversibly to its native state. In order to do this, we used a consensus design approach, analysing a sequence alignment of 212 serpin sequences and determining the prevalent amino acid residue at each position, we termed this serpin conserpin (consensus serpin). Here we present the structural, biophysical and functional characterisation of conserpin. Combined crystallographic and folding studies reveal the characteristics of conserpin that likely dictate its unique stability and folding behaviour, whilst retaining activity as a serine protease inhibitor.