PIGA encodes phosphatidylinositol N-acetylglucosaminyltransferase subunit A, the catalytic subunit of the GPI-N-acetylglucosaminyltransferase complex that catalyzes the first step of glycosylphosphatidylinositol (GPI) anchor biosynthesis 1. This enzyme transfers N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol, initiating GPI anchor assembly on the endoplasmic reticulum membrane. GPI anchors are essential for cell surface expression of complement-regulatory proteins CD55 and CD59 2. PIGA mutations cause disease through two distinct mechanisms. Somatic PIGA mutations in hematopoietic stem cell clones lead to paroxysmal nocturnal hemoglobinuria (PNH), an acquired clonal disorder characterized by hemolytic anemia, thrombosis, and bone marrow failure 1. GPI-deficient erythrocytes lack CD55 and CD59, rendering them susceptible to uncontrolled complement-mediated intravascular hemolysis 3. Clonal expansion occurs through selective advantage when GPI-negative stem cells escape T-cell-mediated autoimmune attack targeting normal hematopoietic cells 4. Conversely, hypomorphic germline PIGA mutations cause multiple congenital anomalies-hypotonia-seizures syndrome 2 and neurodevelopmental disorders with epilepsy 25. PNH is treated with complement-targeted therapy, particularly C5 inhibitors like eculizumab 1, while bone marrow transplantation remains the only cure 2.