VSIG2 (V-set and immunoglobulin domain containing 2) is a membrane-localized immunoglobulin superfamily protein with emerging roles in multiple disease contexts. As a coinhibitory molecule, VSIG2 functions in immune regulation and tumor progression 1. In pancreatic ductal adenocarcinoma, VSIG2 acts as a scaffold protein that simultaneously binds LAMTOR2 and mTOR, enhancing their interaction and promoting mTOR phosphorylation, thereby driving cell proliferation, invasion, and migration 1. VSIG2 is upregulated in PDAC tissues and associated with advanced disease stage and poor survival 1. Beyond cancer, VSIG2 shows disease relevance in osteoclast-mediated osteoporosis, where it is upregulated during osteoclast differentiation and represents a potential therapeutic target 2. VSIG2 exhibits non-linear associations with venous thromboembolism and is involved in endothelium development and atherosclerosis pathways 3. In heart failure with preserved ejection fraction, VSIG2 is downregulated by myeloperoxidase inhibition 4. Additionally, a long noncoding RNA VSIG2-1:1 regulates pulmonary angiogenesis through the VEGF/PI3K/AKT pathway in bronchopulmonary dysplasia 5. VSIG2 is also identified as a dysregulated biomarker in colorectal cancer 6, kidney disease progression 7, and gastric cancer with diagnostic and prognostic potential 8.