PIGH (phosphatidylinositol glycan anchor biosynthesis class H) encodes an essential component of the glycosylphosphatidylinositol N-acetylglucosaminyltransferase (GPI-GnT) complex, catalyzing the transfer of N-acetylglucosamine to phosphatidylinositol in the first step of GPI anchor biosynthesis 1. GPI anchors are glycolipid modifications added to over one hundred human proteins critical for embryogenesis and neurological function 1. PIGH mutations cause glycosylphosphatidylinositol biosynthesis defect 17, a rare autosomal recessive disorder with heterogeneous clinical severity. Mild cases present with developmental delay, hypotonia, and autism without epilepsy 1, while severe cases feature intractable seizures, profound psychomotor retardation, microcephaly, skeletal anomalies including bone fractures and scoliosis, and delayed myelination 2. The p.(Arg163Trp) variant associates with particularly severe manifestations 2. Pathogenic variants range from missense mutations to start-codon disruptions causing truncation at downstream codons 3. Surface expression analysis reveals decreased GPI-anchored proteins on patient cells 12. Additionally, PIGH expression is epigenetically silenced in some B-lymphoblastic leukemia cases, contributing to CD52 loss and alemtuzumab resistance 4. These findings establish PIGH as critical for proper GPI biosynthesis and neurological development.