GPI deficiency is broadly classified into two types: acquired paroxysmal nocturnal hemoglobinuria (PNH) and inherited glycosylphosphatidylinositol (GPI) deficiency (IGD). Both are designated as intractable diseases by the Ministry of Health, Labor and Welfare. PNH is a long-recognized hematological disorder, characterized by hemolytic anemia. Most cases are caused by mutations in the PIGA gene on the X chromosome within hematopoietic stem cells. The number of patients in Japan is estimated to be over 1000. Recently, although extremely rare, cases of PNH involving mutations in PIGT, PIGB, and PIGV have been identified. In these cases, one allele carries a germline mutation, and a somatic mutation occurs in the other allele within hematopoietic stem cells. Notably, PIGT- and PIGB-related PNH are characterized by autoinflammatory symptoms such as meningitis and urticaria [1]. IGD is a hereditary disorder first identified in 2006 [2]. To date, IGD has been linked to mutations in 24 different GPI biosynthesis genes (Fig. 84.1). However, the number of reported patients remains low—approximately 70 in Japan and around 700 worldwide. The clinical symptoms of these disorders have helped clarify the physiological significance of the GPI anchor, marking an important advance in glycoscience.