Life is sustained through the ability of cells to interact with their environment. Underpinning this, is the largest organelle in the cell – the endoplasmic reticulum (ER). As the entry-site to the secretory pathway, it enables thousands of proteins to be displayed on the cell surface, or secreted extracellularly. In addition to its roles in secretion, this organelle handles a plethora of other essential cellular processes, and remarkably, each one is controlled by pairs or families of homologous and parallel machineries. While their homology ensures back-up and robustness in this dynamic organelle, growing evidence points to the fact that each parallel system exerts their own unique functions. To understand the molecular mechanisms that drive this specificity, our lab employs and develops cutting-edge tools aimed at uncovering unique protein interaction landscapes, with a close focus on the discovery of transiently-interacting regulators and substrates. Through this work, we tackle fundamental questions in ER biology, which is crucial for gaining insight into human health and disease.