The stimulation of membrane receptors coupled to the phopholipase C pathway leads to release of Ca2+ from intracellular stores and the resulting depletion of Ca2+ stores triggers in turn the activation of the Ca2+ release activated Ca2+ (CRAC) channels. Recent evidence indicates that ORAI1 is an essential pore subunit of CRAC channels activated by STIM1. Here, we show the genomic organization, tissue expression pattern and functional properties of murine ORAI2 variants in comparison to ORAI1 and ORAI3. The ORAI2 loci were localized in the mice chromosomes 5 and 16 and a long and a short splice variant of ORAI2 (respectively ORAI2L and ORAI2S) was identified and cloned from mice brain. Northern blots revealed a prominent expression of the ORAI2 variants in the brain, lung, thymus and intestine, whilst ORAI1 and ORAI3 appear to be near ubiquitously expressed in mice tissues. The functional properties of ORAI2L and ORAI2S were described and compared to those of ORAI1 in HEK 293 and RBL 2H3 cells that were co-transfected with identical amounts of STIM1 and either cDNA. Our data indicates that ORAI2L and ORAI2S are capable of forming functional CRAC channels in combination with the ubiquitously expressed STIM1.