Plasma membranes encompass a complex and varying set of proteins essential to life. In addition, plasma membrane proteins represent the majority of all known drug targets. The characterization of plasma membrane proteomes is, therefore, of eminent importance. A current bottleneck is the lack of efficient protocols to isolate plasma membranes from tissues or entire organs. To this end, we recently established a simple and effective isolation procedure which is based on aqueous polymer two-phase systems. In this chapter, we provide a detailed protocol for the isolation of plasma membranes from brain tissue, which could easily be adapted to other sources.
