PIGU (phosphatidylinositol glycan anchor biosynthesis class U) is a critical subunit of the glycosylphosphatidylinositol transamidase (GPI-T) complex that catalyzes GPI-anchor attachment to proteins in the endoplasmic reticulum 1. PIGU binds the lipid portion of GPI-anchors and acts as an organizer in the transmembrane layer to recruit other complex subunits, essential for GPI-anchored protein biosynthesis 1. Beyond its canonical GPI-anchor function, PIGU is highly overexpressed in multiple cancers. In hepatocellular carcinoma (HCC), PIGU promotes progression through PI3K/AKT and NF-κB pathway activation, enhancing cell proliferation, migration, and immune evasion 23. PIGU upregulation modulates glycolytic metabolism, affecting glucose conversion to pyruvate and cell cycle progression 3. In esophageal squamous cell carcinoma, PIGU knockdown reduces migration, invasion, and induces apoptosis through epithelial-mesenchymal transition suppression 4. PIGU serves as an independent prognostic biomarker in HCC, improving risk stratification beyond TNM staging 5. In colorectal cancer with KRAS mutations, low PIGU expression correlates with poor prognosis 6. PIGU is recognized as an intrinsic immune-evasion gene, contributing to immune escape and therapeutic resistance 78. Clinically, PIGU represents a promising diagnostic and therapeutic target for multiple malignancies.