PIGB encodes an alpha-1,2-mannosyltransferase essential for glycosylphosphatidylinositol (GPI) anchor biosynthesis, catalyzing the transfer of the third mannose residue from dolichol-phosphate-mannose to GPI intermediates in the endoplasmic reticulum 1. This enzyme participates in the ninth step of GPI anchor biosynthesis, enabling proper cellular localization and function of GPI-anchored proteins 1. Pathogenic variants in PIGB cause early infantile epileptic encephalopathy 80 (EIEE-80), characterized by severe developmental delay, early-onset epilepsy, peripheral neuropathy, and hypomyelination 2. The disorder also encompasses acrofrontofacionasal dysostosis type 1 (AFFND1), featuring dysmorphic features, skeletal abnormalities, and intellectual disability 1. Germline PIGB mutations can contribute to paroxysmal nocturnal hemoglobinuria (PNH) through copy-neutral loss of heterozygosity, resulting in complement-mediated hemolysis and inflammatory symptoms 34. Unlike typical PIGA-related PNH, PIGB-deficient cells accumulate GPI intermediates on the cell surface, which together with complement activation cause inflammasome activation and auto-inflammatory features 4. Clinical presentation ranges from severe neurodevelopmental disorders to hematological manifestations, expanding the phenotypic spectrum of GPI biosynthesis defects.