Soon after Gorter and Grendel proved the existence of lipid bilayers, it became obvious that proteins were also a component of membranes. It is a protein’s amino acid sequence that locates it to membranes. Hydropathy Plots are used to predict which segments of a protein cross the membrane. It is not clear how many distinct types of membrane proteins exist. A first crude approach identifies peripheral (loosely attached to the membrane surface by electrostatics) and integral (penetrates into the hydrophobic interior). Integral proteins span membranes via two major structures, α-helices or β-barrels. α-Helices can cross the membrane single or multiple times. A very large family of proteins, including G-protein-coupled receptors, have 7 membrane-spanning α-helices. β-Barrels are composed of 20 or more β-sheet segments that line a membrane-spanning cylinder. Many integral proteins are also anchored to the membrane cytoplasmic surface by lipids, primarily myristic, palmitic, or prenyl groups. Some outer surface proteins are anchored through the acyl chains of glycosylphosphatidylinositol (GPI). Most membrane surface proteins are heavily glycosylated.