Store-operated calcium entry channel (SOCE)

Store-operated calcium entry (SOCE) is a vital cellular mechanism that replenishes intracellular calcium stores and facilitates sustained calcium signaling (Prakriya & Lewis, 2015). The process is primarily mediated by the Calcium Release-Activated Calcium (CRAC) channel, a complex formed by the endoplasmic reticulum (ER) calcium sensor STIM1 and the plasma membrane pore-forming protein Orai1 (Feske et al., 2006). When ER calcium levels drop—often following IP3-mediated release—STIM1 proteins aggregate and activate Orai1 channels, allowing extracellular calcium to enter the cytoplasm (Stauderman, 2018). This pathway is essential for the activation of NFAT and subsequent gene expression in immune cells, as well as for maintaining calcium homeostasis in non-excitable cells (Feske, 2007). Dysfunctional SOCE is linked to various conditions, including severe combined immunodeficiency, autoimmune diseases, and certain cancers where it promotes cell migration and proliferation (Stauderman, 2018). Pharmacological targeting of SOCE, particularly through Orai1 inhibitors like Auxora (CM4620), is currently being explored for treating acute pancreatitis and other inflammatory disorders (CalciMedica, 2024).

Other names

Calcium release-activated calcium channelCRAC channelOrai1/STIM1 complexCapacitative calcium entry pathwayIP3-dependent calcium entry pathway

Inhibition of the Orai1 pore or disruption of the STIM1-Orai1 interaction to prevent calcium influx.