Highly efficient mechanisms regulate intracellular calcium (Ca 2+ ) levels. The recent discovery of new components linking intracellular Ca 2+ stores to plasma membrane Ca 2+ entry channels has brought new insight into the understanding of Ca 2+ homeostasis. Stromal interaction molecule 1 (STIM1) was identified as a Ca 2+ sensor essential for Ca 2+ store depletion-triggered Ca 2+ influx. Orai1 was recognized as being an essential component for the Ca 2+ release-activated Ca 2+ (CRAC) channel.

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... gether, these proteins participate in store-operated Ca 2+ channel function. Defective regulation of intracellular Ca 2+ is a hallmark of several diseases. In this review, we focus on Ca 2+ regulation by the STIM1/Orai1 pathway and review evidence that implicates STIM1/ Orai1 in several pathological conditions including cardiovascular and pulmonary diseases, among others.