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Paroxysmal nocturnal hemoglobinuria (PNH) is a disease caused by a phosphatidylinositol glycan anchor biosynthesis class A (PIG-A) mutation in hematopoietic stem cells. There are three theories about the possible mechanism of the pathogenesis of PNH: immune escape, anti-apoptotic mechanism, and secondary gene mutation. There has been little gain in the knowledge regarding its pathogenesis during the last decade owing to the lack of representative cell lines and animal models. There have been recent reports about the successful creation of PNH mouse and PNH rhesus macaque models. The detection of glycosylphosphatidylinositol-anchor protein (GPI-AP)-deficient cells and/or fluorescently labeled variant of aerolysin (FLAER) test, estimation of erythrocyte life span, and hemolysis-related experiments demonstrated that these animal models of PNH had GPI-AP-deficient blood cells with shortened lifespans and increased sensitivity to complement-activated hemolysis. However, there were no clinical manifestations such as hemolysis and thrombosis in these animal models. This suggested that the PIG-A mutation is one of the several conditions required for PNH, but it alone is not enough to cause PNH. [ABSTRACT FROM AUTHOR]