Stromal interaction molecule 2 (STIM2) (STIM2)

Stromal interaction molecule 2 (STIM2) is a transmembrane protein located in the endoplasmic reticulum (ER) that serves as a high-sensitivity sensor of luminal calcium levels (UniProt Q9P243). Unlike its homolog STIM1, which responds to massive calcium depletion, STIM2 is activated by subtle fluctuations in ER calcium, making it a key regulator of basal calcium levels and resting store-operated calcium entry (SOCE) (Brandman et al., 2007). Upon sensing reduced ER calcium, STIM2 undergoes a conformational change and translocates to ER-plasma membrane junctions, where it recruits and activates Orai1 calcium channels (Stathopulos et al., 2009). This process is critical for maintaining intracellular calcium homeostasis, particularly in neurons where it supports synaptic plasticity and dendritic spine maintenance (Berna-Erro et al., 2009). Dysregulation of STIM2-dependent SOCE has been implicated in neurodegenerative conditions like Alzheimer's disease, where loss of STIM2 leads to synaptic failure, as well as in certain cancers and autoimmune disorders (Sun et al., 2014; Sobradillo et al., 2014). Pharmacological targeting of STIM2 aims to restore calcium balance, though achieving selectivity over STIM1 remains a significant therapeutic challenge (Bird et al., 2011).

Other names

GOK2Stromal interaction molecule 2STIM2-dependent store-operated Ca2+ entrySTIM2-dependent SOCE

STIM2 acts as a sensitive sensor of endoplasmic reticulum (ER) calcium; upon store depletion, it translocates to the plasma membrane to recruit and activate Orai1 channels, facilitating store-operated calcium entry (SOCE) to maintain cellular calcium homeostasis.