Antigen stimulation of immune cells triggers Ca++ entry through Ca++ release-activated Ca++ (CRAC) channels (1 for review). ORAI1 is a recently identified four-transmembrane spanning protein that is an essential component of CRAC. A missense mutation in this protein in humans is the cause of one form of hereditary severe combined immune deficiency (SCID) which results in ablated T-cell Ca++ entry (2). It has been suggested that ORAI1 functions as a highly selective Ca++ plasma membrane channel that is gated through interactions with STIM1, the store-activated endoplasmic reticulum Ca++ sensor (3). ORAI1 often migrates at a higher than expected molecular weight in SDS-PAGE.