Toxin entry: how reversible is the secretory pathway?

A number of proteins produced by plants and bacteria are extremely toxic to eukaryotic cells. Their potency arises from their ability to catalyse the modification of crucial cellular components. Only a few toxin molecules are required to kill a cell, but to do so they must first reach the cytosol. How such proteins are translocated across the target cell membrane is poorly understood, but we argue here that some toxins may travel the secretory pathway in reverse, passing all the way from the cell surface to the endoplasmic reticulum (ER) before entering the cytosol.