PIGL encodes a key enzyme in glycosylphosphatidylinositol (GPI) anchor biosynthesis, catalyzing the de-N-acetylation of N-acetylglucosaminyl-phosphatidylinositol in the endoplasmic reticulum. Beyond its canonical metabolic role, PIGL exhibits dual subcellular localization with distinct functions: cytoplasmic PIGL participates in GPI biosynthesis, while nuclear PIGL acts as a tumor suppressor by disrupting the cMyc/BRD4 transcriptional axis, reducing expression of immunosuppressive chemokines CCL2 and CCL20 1. PIGL phosphorylation at Y81 by FGFR2 retains the protein in the cytosol, promoting tumor immune evasion 1. The protein is essential for placental development, particularly syncytiotrophoblast differentiation, and its deficiency triggers excessive unfolded protein response and impairs WNT signaling 2. PIGL mutations cause two distinct autosomal recessive disorders: CHIME syndrome (colobomas, heart defects, ichthyosiform dermatosis, intellectual disability, ear anomalies) and Mabry syndrome (hyperphosphatasia with mental retardation syndrome) 3 4. The gene's high Alu repeat content (~34% of intronic sequence) predisposes it to deletion mutations 5. Recent genome-wide association studies have also identified PIGL as a potential novel risk locus for Parkinson's disease 6.