Store operated calcium entry (SOCE) is a ubiquitous mechanism that ensures the refilling of the calcium stores, mainly the endoplasmic reticulum (ER) after depletion (1). A reduction of ER calcium content is sensed by STIM1 protein which translocates into subplasmalemmal puncta upon store depletion where it activates Orai channels and triggers calcium influx (2). In the pancreatic acinar cell, a well established model of exocrine secretory epithelium, enzyme secretion is driven by localised calcium oscillations. The main Ca²⁺ release sites – IP₃ receptors – are located in the apical region of the ER (3). Our experiments on primary murine pancreatic acinar cells show that when the ER calcium store is depleted by continuous physiological or pathological stimulation STIM1 translocates towards the basal and lateral membranes only avoiding the apical pole. This indicates that different ER compartments are specialised in separate Ca²⁺ handling functions. Spatial segregation of intracellular Ca²⁺ release and Ca²⁺ reloading ensures minimal interference and maximum efficiency of both processes in this highly specialised cell type. The most controversial aspect of this finding is that in pancreatic acinar cells the basal and lateral regions contain rough endoplasmic reticulum. The distance permissive for physical interaction between STIM and Orai proteins is significantly smaller than the size of an average ribosome that decorates the surface of the ER in these cells (4). We resolved this paradox by identifying ribosome free ER terminals forming junctions between the plasma membrane and the rough ER in the basol-lateral regions.