From a mechanistic perspective, the FR functions to concentrate exogenous ligands (e.g. folates and folate-drug conjugates) into the cell cytosol by endocytosis.[1] The term endocytosis refers to the process whereby the plasma membrane invaginates and eventually forms a distinct intracellular compartment. The endocytic vesicles (endosomes) rapidly become acidified to allow the FR to release its ligand.[13] Afterwards, the empty FR returns to the cell surface where it can participate in another round of ligand-mediated endocytosis.[14]