In non-excitable cells such as T lymphocytes,hepatocytes,mast cells,endotheliaand epithelia,the major pathway for calcium(Ca~(2+))entry is through store-oper-ated Ca~(2+)channels in the plasma membrane.These channels are activated by theemptying of intracellular Ca~(2+)stores,however,neither the gating mechanism northe downstream targets of these channels has been clear established.Here,Ireview some of the proposed gating mechanisms of store-operated Ca~(2+)channelsand the functional implications in regulating pro-inflammatory signals. In non-excitable cells such as T lymphocytes, hepatocytes, mast cells, endothelia and epithelia, the major pathway for calcium (Ca2 +) entry is through store- oper-ated Ca2 + channels in the plasma membrane These channels are activated by theemptying of intracellular Ca ~ 2 stores, however, neither the gating mechanism northe downstream targets of these channels has been clear established. Here, Ireview some of the proposed gating mechanisms of store-operated Ca ~ ( 2+) channels and the functional implications in regulating pro-inflammatory signals.