PIGM (phosphatidylinositol glycan anchor biosynthesis class M) encodes the catalytic subunit of glycosylphosphatidylinositol (GPI)-mannosyltransferase I, which catalyzes transfer of the first mannose residue to GPI core structures during GPI anchor biosynthesis 1. This enzymatic activity is essential for generating mature GPI anchors that tether numerous cell surface proteins including co-receptors, enzymes, and adhesion molecules to lipid rafts 1. PIGM transcription is tightly regulated by the generic transcription factor Sp1, with cell-type-specific chr1 accessibility determining tissue-specific expression patterns 2. Mutations in PIGM cause inherited glycosylphosphatidylinositol deficiency (IGD), a rare congenital disorder of glycosylation with heterogeneous clinical presentations 3. PIGM promoter mutations associate with intractable epilepsy, intellectual disability, and thrombotic complications including portal and cerebral vein thrombosis 34. Coding variants in PIGM cause more severe phenotypes, including cystic encephalomalacia and progressive neurodegeneration 5. Sodium phenylbutyrate shows therapeutic promise in managing certain PIGM-deficiency presentations 3. Understanding PIGM regulation and function provides insights into GPI-anchor biosynthesis and potential treatment strategies for GPI-related disorders.