PIGN (phosphatidylinositol glycan anchor biosynthesis class N) encodes an ethanolamine phosphate transferase that catalyzes a critical step in GPI-anchor biosynthesis by transferring ethanolamine phosphate to mannosyl intermediates [UniProt]. This enzyme functions in the endoplasmic reticulum and participates in the eighth step of GPI-anchor assembly, essential for anchoring proteins to the cell membrane. Beyond its canonical role in GPI biosynthesis, PIGN functions as a regulator of mitotic integrity. PIGN gene expression aberrations, characterized by partial intron retention causing frameshifts and premature termination, correlate with increased genomic instability and myelodysplastic syndrome progression 1. PIGN protein interacts with spindle assembly checkpoint protein MAD1 and regulates its expression during cell cycle progression, maintaining chr18 stability independent of TP53 pathways 1. Pathogenic PIGN mutations cause Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 1, reflecting the essential role of GPI-anchored proteins in development [NCBI Summary]. Additionally, PIGN is implicated in cardiomyopathies associated with inherited metabolic carbohydrate disorders, indicating cardiac complications may arise from disrupted GPI-anchor biosynthesis 2. Loss of PIGN function leads to GPI-anchor protein deficiency, which directly compromises cell surface protein localization and function, explaining the pleiotropic clinical manifestations observed in PIGN-related disorders.