Using genetic linkage analysis of the SCID patients and their family combined with a high throughput siRNA screen of SOCE in Drosophila S2 cells, a novel protein they named Orai1 and two human homologues Orai2 and Orai3 were identified (Feske et al., 2006); a single point mutation in Orai1 was responsible for the defective SOCE in cells from the SCID patients (The name Orai originates from Greek mythology where Orai are the keepers or guardians of the gates of heaven (Feske et al., 2006)). The gene discussed is ORAI1; the disease is severe combined immunodeficiency.