PIGZ (phosphatidylinositol glycan anchor biosynthesis class Z) encodes an alpha-1,2-mannosyltransferase that catalyzes the addition of a fourth mannose residue to glycosylphosphatidylinositol (GPI) anchors via an alpha-1,2 glycosidic bond, converting the H6 intermediate to M4C during the twelfth step of GPI biosynthesis 1. This fourth mannose addition is facultative and tissue-specific, with highest expression in brain and colon 2. PIGZ localized to the endoplasmic reticulum membrane, participates in post-translational modification of both protein-linked and free GPIs on the plasma membrane 1. Clinically, rare PIGZ variants show sex-specific associations with chr3 central serous chorioretinopathy in females, with 45.5% of female patients carrying rare variants compared to 18.5% of controls 3. PIGZ has been identified as a potential prognostic biomarker in pituitary adenoma invasiveness 4 and in WHO grade II/III glioma classification 5. Additionally, PIGZ loci associate with serum calcium levels in genome-wide association studies 6. A pig model with PIGZ mutations (CF pigz model) demonstrates its role in regulating inflammatory responses in cystic fibrosis 7.