We are investigating how and why disease-related differences in the asthma gene, ADAM33, lead to airway ‘twitchiness’ This characteristic feature of asthma is caused by airways that narrow too much and too easily in response to harmless stimuli, leading to typical symptoms of wheeze, shortness of breath and cough. Our discovery of ADAM33 came from a five year collaborative genetic study, where we found that small changes in the ADAM33 gene occurred in people with asthma and these changes were particularly associated with the degree of airway ‘twitchiness’. Although inflammation is an important component of asthma, it has recently been shown that an alteration in the structure (remodelling) of the airways is also important. As ADAM33 appears to act in the structural cells, rather than in inflammatory cells, we predict that ADAM33 causes airway remodelling. If we are correct, this offers the potential for development of new therapies distinct from those such as steroids that damp down the inflammatory response. By targeting the function of a gene close to the origin of asthma, this should make a major impact on our understanding of the factors that underlie this common disease and enable design of better prevention and intervention strategies.