ORAI1 and immune system disorder: Genetic defects in extracellular Ca2+ influx have been formally associated with primary immunodeficiency, with defects in the store-operated Ca2+ entry stage of Ca2+ signaling through the demise or loss-of-function of ORAI1 or STIM1 causing severe immunodeficiency [18–20] and defective nuclear translocation of NFAT blocking the production of cytokines, resulting in immunodeficiency [21].