CD47 is a widely expressed transmembrane glycoprotein that functions as an innate immune checkpoint. It acts as a universal "self" marker by binding to signal regulatory protein alpha (SIRPα) on macrophages and other myeloid cells, transmitting an inhibitory ("don't eat me") signal that prevents phagocytosis of healthy cells. Many cancers exploit this protective mechanism by overexpressing CD47 to evade immune surveillance. Blocking the CD47-SIRPα interaction releases this inhibition, enabling macrophages to recognize and engulf tumor cells, making CD47 a promising target in cancer immunotherapy. However, its broad expression, particularly on RBCs and platelets, presents a significant challenge for therapeutic targeting.