ORAI1 and immunodeficiency disease: Patients with null or loss-of-function mutations in ORAI1 present with a complex disease syndrome, CRAC channelopathy, which is characterized by immunodeficiency, autoimmunity, muscular hypotonia and ectodermal dysplasia because ORAI1 has critical functions in T cells, skeletal muscle cells, dental enamel-forming cells and eccrine sweat glands17, 18, 19.