Abstract
• Cellular Ca 2+ signaling is fine-tuned by a set of Ca 2+ sensitive protein to control a variety of biological functions. • The rhomboid intramembrane protease RHBDL2 can downregulate abnormal Ca 2+ entry via CRAC channels. • RHBDL2 is sensitive to elevations in intracellular Ca 2+ concentrations and the presence of a proline in the TM domain containing the rhomboid cleavage site. • The gain-of-function mutant Orai1 P245L linked to the stormorken syndrome is defective in RHBDL2 mediated cleavage.
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