CD59 is a membrane-bound complement regulatory protein that protects cells from damage during complement activation 1. Functionally, CD59 inhibits membrane attack complex (MAC) assembly by binding to the pore-forming β-hairpins of C8 and deflecting C9 monomers, preventing their membrane insertion and polymerization into lytic pores 2. This dual mechanism—blocking C8 insertion and redirecting C9 trajectory—halts MAC formation downstream of C5b-8 intermediates 3. CD59 is particularly essential for protecting hematopoietic and neuronal tissues 1. Loss-of-function mutations cause CD59 deficiency, characterized by complement-mediated hemolytic anemia and severe neurological complications including recurrent demyelinating neuropathy and stroke, affecting 100% and 92% of patients respectively 4. In paroxysmal nocturnal hemoglobinuria (PNH), somatic PIGA mutations prevent GPI-anchor synthesis, eliminating CD59 surface expression on red blood cells and causing intravascular hemolysis, thrombosis, and potential mortality 56. Additionally, cancer cells exploit CD59 upregulation via EGFR/Wnt signaling to suppress complement-mediated immune activation and evade CD8+ T cell responses 7. Clinically, CD59 loss-of-function demonstrates the critical importance of complement regulation in maintaining cellular integrity and immune homeostasis, with complement inhibition providing therapeutic benefit in both genetic deficiency and acquired complement disorders.