The importance of protease activity to allergenicity and the progression of allergic disease is supported by a growing range of evidence which may be briefly summarised thus: (i) facilitation of inhalant allergen detection by antigen presenting cells; (ii) activation of signal transduction mechanisms which drive innate immune responses to break tolerance and promote the acquisition of allergic sensitisation; and (iii) more chronically, activation of IgE-independent mechanisms which result in cellular transitions and airways pathophysiology of variable reversibility. This evidence concerns the gene IGHE and allergic disease.