PIGC encodes a component of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex, which catalyzes the initial and rate-limiting step of GPI anchor biosynthesis by transferring N-acetylglucosamine to phosphatidylinositol 1. GPI anchors tether numerous cell surface proteins to the plasma membrane, and PIGC deficiency results in reduced surface expression of GPI-anchored proteins as demonstrated by flow cytometry analysis 12. Biallelic PIGC mutations cause a severe neurodevelopmental disorder characterized by global developmental delay, intellectual disability, and early-onset treatment-resistant seizures 12. A cohort of 18 probands with PIGC variants exhibited severe cognitive impairment, seizures, hypotonia, and brain imaging abnormalities, with premature death occurring in 10 cases (median age 40 months) 2. These clinical features define glycosylphosphatidylinositol biosynthesis defect 16, classified as a congenital disorder of glycosylation 3. Beyond neurological disease, PIGC expression is upregulated in hepatocellular carcinoma and correlates with poorer overall survival and increased immune cell infiltration, suggesting potential roles in cancer progression and immunity 4. A genome-wide association study identified suggestive association between a DNM3-PIGC locus variant and MS severity, implicating CNS resilience in neurological progression 5.