The contribution of systematic approaches to characterizing the proteins and functions of the endoplasmic reticulum

The endoplasmic reticulum (ER) is a complex organelle responsible for a range of functions including protein folding and secretion, lipid biosynthesis, and ion homeostasis. Despite its central and essential roles in eukaryotic cells during development, growth, and disease, many ER proteins are poorly characterized. Moreover, the range of biochemical reactions that occur within the ER membranes, let alone how these different activities are coordinated, is not yet defined. In recent years, focused studies on specific ER functions have been complemented by systematic approaches and innovative technologies for high-throughput analysis of the location, levels, and biological impact of given components. This article focuses on the recent progress of these efforts, largely pioneered in the budding yeast Saccharomyces cerevisiae, and also addresses how future systematic studies can be geared to uncover the "dark matter" of uncharted ER functions.