PIGG encodes the catalytic subunit of ethanolamine phosphate transferase 2, which catalyzes the transfer of ethanolamine phosphate from phosphatidylethanolamine to the sixth position of the second alpha-1,6-linked mannose during glycosylphosphatidylinositol (GPI) anchor biosynthesis 1. This enzyme catalyzes the eleventh step of GPI anchor synthesis, generating mature anchors that tether surface proteins to cell membranes. GPI-anchored proteins are essential for cellular functions including immune signaling and cell adhesion. Pathogenic PIGG variants cause inherited GPI deficiency (IGD), characterized by variable neurological manifestations depending on enzymatic activity levels 1. Individuals with null or severely decreased PIGG activity present with hypotonia, intellectual disability/developmental delay, seizures, cerebellar atrophy, and mitochondrial dysfunction, while those with mildly decreased activity exhibit autism spectrum disorder 1. Fibroblasts from affected individuals show decreased surface levels of the GPI-anchored protein CD73 1. Recent epigenetic studies identified hypomethylated PIGG loci associated with incident acute coronary syndrome, with increased leukocyte expression in atherosclerotic plaques, suggesting roles beyond neurological disease 2. Clinical diagnosis is facilitated by whole-genome sequencing, which outperforms conventional testing in identifying PIGG variants 3. Understanding PIGG function advances knowledge of GPI biosynthesis-related neurological disorders and potential cardiovascular disease mechanisms.