PIGY encodes a component of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the first step of GPI anchor biosynthesis by transferring N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol 1. The protein may function by regulating the catalytic subunit PIGA within this complex 1. PIGY mutations cause hyperphosphatasia with impaired intellectual development syndrome 6, characterized by variable phenotypes ranging from severe multi-system disease with dysmorphism, seizures, developmental delay, cataracts and early death to milder forms with moderate developmental delay and microcephaly 2. Pathogenic variants can occur in both coding regions, such as c.137T>C (p.Leu46Pro), and non-coding regulatory regions like promoter variants that disrupt transcription factor binding sites 2. Patient-derived fibroblasts show significantly reduced GPI-anchored proteins (CD55 and CD59) on cell surfaces, confirming functional impairment 2. Additionally, PIGY transcriptional silencing through hypermethylation has been observed in Burkitt lymphoma cell lines, contributing to GPI anchor deficiency in these cancer cells 3. The gene has also been identified as a hub gene associated with immune recovery in HIV patients 4.