By re-examining previous studies in immune and non-immune cells from humans, mouse models and even lower organisms (e.g. yeast), we attempt to elucidate potential mechanisms by which ORMDL3 overexpression in CD4+ T cells may connect to enhanced pathophysiology of asthma in patients carrying the 17q12-21 risk SNPs. The gene discussed is ORMDL3; the disease is asthma.