LRIG1 is a transmembrane protein that functions as a negative regulator of receptor tyrosine kinase (RTK) signaling through enhancement of receptor ubiquitination and degradation 1. Beyond its classical role in RTK antagonism, LRIG1 operates as a pleiotropic tumor suppressor regulating stem cell quiescence across multiple tissues 1. In colonic stem cells, LRIG1 marks hyperproliferative cancer stem cells driven by oncogenic mutations, distinguishing them from fibroblast-induced quiescent stem cells 2. LRIG1 also functions as an immune checkpoint receptor by binding VISTA, suppressing T cell receptor signaling in CD8+ tumor-infiltrating lymphocytes 3. In intestinal inflammation, macrophage-derived VISTA engages LRIG1 on intestinal stem cells to suppress PPARα signaling, impairing epithelial repair in colitis 4. Clinically, LRIG1 expression serves as a prognostic biomarker; reduced expression correlates with poor survival in breast cancer, nasopharyngeal carcinoma, and other malignancies 5. LRIG1 is predominantly expressed in epithelial tissues and scattered neurons as an integral cell-surface protein 6. These findings support developing LRIG1-based therapeutics and targeting the VISTA/LRIG1 axis for cancer immunotherapy and inflammatory bowel disease treatment.