Functional communication between IPR and STIM2 at subthreshold stimuli is a critical checkpoint for initiation of SOCE.

Stromal interaction molecules, STIM1 and STIM2, sense decreases in the endoplasmic reticulum (ER) [Ca] ([Ca]) and cluster in ER-plasma membrane (ER-PM) junctions where they recruit and activate Orai1. While STIM1 responds when [Ca] is relatively low, STIM2 displays constitutive clustering in the junctions and is suggested to regulate basal Ca entry. The cellular cues that determine STIM2 clustering under basal conditions is not known.