Selective knockdown of ORMDL3 in lung epithelial cells leads to airway hyperresponsiveness [48], while downregulation of ORMDL3 in mast cells, cells key to asthma pathogenesis, enhances antigen mediated expression of proinflammatory cytokines and production of prostaglandin D2 and promotes mast cell driven inflammation in vivo [49]. The gene discussed is ORMDL3; the disease is airway hyperresponsiveness.