Ca2+ influx is essential for a variety of cellular functions including, secretion and transcription. Stromal interaction molecule 1 (Stim1) is a ubiquitously expressed cell surface transmembrane glycoprotein that plays a role in medi-ating Ca2+ influx following the depletion of intracellular Ca2+ stores. Stim1 functions in the endoplasmic reticulum (ER) where it acts as a Ca2+ sensor via its EF-hand domain which causes large conformational changes. When Ca2+ levels drop, Stim1 translocates from the ER to the plasma membrane, where it activates the Ca2+ release-activated Ca2+ (CRAC) channel subunit, TMEM142A/Orai1. Stim2 is a potent inhibitor of Stim1-mediated store-operated calcium (SOC) entry. Stim1 is implicated in tumor growth suppression and stromal-hematopoietic cell interactions.