Aire has been cloned as the gene responsible for a hereditary type of organ‐specific autoimmune disease. Aire controls the expression of a wide array of tissue‐restricted Ags by medullary thymic epithelial cells (mTECs), thereby leading to clonal deletion and Treg‐cell production, and ultimately to the establishment of self‐tolerance. However, relatively little is known about the mechanism responsible for the control of Aire expression itself. In this issue of the European Journal of Immunology, Haljasorg et al. [Eur. J. Immunol. 2015. 45: 3246–3256] have reported the presence of an enhancer element for Aire that binds with NF‐κB components downstream of the TNF receptor family member, RANK (receptor activator of NF‐κB). The results suggest that RANK has a dual mode of action in Aire expression: one involving the promotion of mTEC differentiation and the other involving activation of the molecular switch for Aire within mature mTECs.