Cartoon view of STIM1 in an extended conformation, bridging the distance from ER to plasma membrane. For clarity, a single STIM monomer is shown, but the active extended form in cells is oligomeric. Functional regions of STIM discussed in the text are the calcium-sensing EF-SAM domain in the ER lumen, the cytoplasmic CC1 region that both stabilizes inactive STIM and transmits the activating conformational change upon ER calcium store depletion, the SOAR/CAD domain that recruits and gates ORAI channels, and the polybasic tail that interacts with plasma membrane phosphoinositides.