Eukaryotic cells target a large fraction of proteins synthesized in the cytosol to a number of different intracellular membrane compartments (organelles). Membrane targeting information is typically contained in hydrophobic signal sequences, which specify the organellar destination of proteins they are attached to. These molecular zipcodes are read out by specialized chaperones, called targeting factors (TFs), which tightly bind to them soon after they emerge from the ribosome. Upon encountering TF receptors on the cytosolic surface of organelles, TFs let go of their substrates, thus enabling them to be inserted into or translocated across organellar membranes. Our understanding of how TF receptors disrupt TF-substrate complexes is still rudimentary. Read more.