Recently, through genome wide high-throughput RNA interference screens and analysis of patients with severe combined immunodeficiency (SCID), a pore-forming plasma membrane protein, ORAI1 (Feske et al., 2006; Vig et al., 2006; Zhang et al., 2006), and an ER Ca2+ sensing molecule, stromal interaction molecule 1 (STIM1) (Liou et al., 2005; Roos et al., 2005), have been identified as the classically defined CRAC channel. The gene discussed is ORAI1; the disease is severe combined immunodeficiency.