STIMATE (STIM activating enhancer) is a regulatory protein that functions as a key modulator of store-operated calcium entry (SOCE) at endoplasmic reticulum-plasma membrane (ER-PM) junctions. SOCE is a calcium influx mechanism activated following depletion of intracellular calcium stores 1. STIMATE operates by interacting with STIM1, a master regulator of calcium signaling, to promote STIM1 conformational changes necessary for its activation 1. The protein plays a critical role in STIM1 relocalization to ER-PM junctional sites, specialized contact zones that mediate calcium entry 2. Beyond acute signaling, STIMATE contributes to the long-term maintenance and structural reorganization of store-dependent ER-PM junctions 2. This function is essential for sustained calcium homeostasis in cells. The calcium signaling pathway regulated by STIMATE is fundamental to numerous cellular processes including immune cell activation, muscle contraction, and gene transcription. Dysregulation of SOCE has been implicated in various pathologies including immunodeficiency, muscle disorders, and cancer. STIMATE's role as an enhancer of STIM1-mediated calcium entry positions it as a potential therapeutic target for conditions involving impaired calcium signaling.