The gene was first reported by two independent research groups Aaltonen et al. and Nagamine et al. in 1997 who were able to isolate and clone the gene from human chromosome 21q22.3. Their work was able to show that mutations in the AIRE gene are responsible for the pathogenesis of Autoimmune polyglandular syndrome type I. More insight into the Aire protein was later provided by Heino et al. in 2000. They showed that Aire protein is mainly expressed in the thymic medullary epithelial cells using immunohistochemistry.