Store-operated calcium channel protein (SOCE channel (or CRAC channel, for the best-characterized subtype))

Store-operated calcium entry channels are a family of plasma membrane ion channels that mediate Ca²⁺ influx into cells following depletion of endoplasmic reticulum (ER) Ca²⁺ stores. The best-characterized molecular components are the stromal interaction molecule 1/2 (STIM1/2), which act as ER-resident Ca²⁺ sensors, and Orai proteins (Orai1/2/3), which form highly selective Ca²⁺ channels at the plasma membrane known as CRAC channels. Upon ER store depletion—often triggered by receptor-mediated activation—STIM proteins translocate toward ER-plasma membrane junctions where they physically interact with and activate Orai channels, allowing extracellular Ca²⁺ influx. This process is essential for diverse physiological functions including gene expression control, immune cell activation via NFAT signaling pathways, exocytosis/secretion events, neuronal excitability modulation, and maintenance of overall cellular calcium homeostasis.[1][2][3][4] Dysregulation or genetic defects affecting these components can result in severe immunological disorders or contribute to neurological/cardiovascular pathologies.[4]

Other names

Store-operated calcium entry channelStore-operated calcium channel (SOC)Calcium release-activated calcium channel (CRAC)Orai1/STIM1 complexSOCE complex

Drugs targeting this molecule typically act as inhibitors of the Orai1/STIM1 interaction or block the pore-forming activity of Orai channels to reduce store-operated Ca²⁺ influx.