Based on limited published evidence, GRAMD2A is a constitutive tether protein that organizes endoplasmic reticulum-plasma membrane contact sites (EPCS) through phosphatidylinositol lipid-dependent mechanisms. GRAMD2A co-localizes with ESYT2/3 tethers and pre-marks PI(4,5)P2-enriched EPCS destined for store-operated calcium entry, facilitating STIM1 recruitment 1. As a GRAM domain protein, GRAMD2A functionally specializes distinct ER-PM domains and exhibits pleiotropic roles in calcium homeostasis and organelle dynamics 1. GRAMD2A ablation impairs STIM1 translocation at these specialized contact sites 2.