E-Syt1 and E-Syt2 are required for full activation of SOCE in ER+ breast cancer MCF7 cells and the TNBC cell lines MDA-MB-231 and BT20, most likely by supporting the close apposition of Orai1 and STIM1 in ER–PM junctions. The gene discussed is ORAI1; the disease is breast carcinoma.