Biological membranes form selectively permeable barriers that play a central role in maintaining the unique chemical environment of cells and subcellular compartments. Proteins embedded in membranes enforce selective permeability, thus they facilitate the spatial and temporal separation of physiological activities central to normal cell function and multicellular organization. Membrane proteins mediate crucial processes such as signaling between cells, transport across membranes, and energy transduction. Consistent with their essential roles, defects in membrane proteins result in a variety of pathological conditions. Consequently, these proteins are the focus of numerous pharmaceutical drug development programs, and more than 50% of drugs in use today target membrane proteins. Despite their importance, we lack a structural and mechanistic understanding of the various processes mediated by membrane proteins. One of the big questions is “how do ions, molecules and information traverse membranes?  We seek answers to this question by studying specialized membrane proteins such as receptors, ion channels, and transporters using x-ray crystallographic, biochemical and biophysical approaches.