Red blood cell (RBC) formation in mammals requires the enucleation of late-stage erythroblasts. This process is now recognized to be a multistep one that includes (1) eccentric positioning of the nucleus associated with a microtubule network, (2) the pinching of the erythroblast associated with a localized actin-myosin ring and lipid rafts, as well as endocytic vesicle formation (not shown), and (3) the formation of 2 cells: a pyrenocyte that is rapidly engulfed by macrophage cells and a reticulocyte that continues to mature into a biconcave RBC.