VSIG1 (V-set and immunoglobulin domain containing 1) is a cell-cell adhesion molecule of the immunoglobulin superfamily that functions as a tumor suppressor in multiple cancer types 1. The protein is normally expressed in gastric mucosa and testis, and forms homodimers through homophilic cis-interactions 1. In gastric cancer, VSIG1 serves as a specific marker of gastric phenotype and is directly correlated with MUC5AC expression 2. High VSIG1 expression is associated with better overall survival in gastric cancer patients (hazard ratio 0.58) and functions as an independent favorable prognostic factor 1. The protein exerts tumor suppressive effects by reducing cell proliferation, migration, and invasion in gastric, lung, and esophageal cancer cells 1. VSIG1 is involved in epithelial-mesenchymal transition regulation, where its subcellular translocation from membrane to cytoplasm indicates EMT activation through the canonical Wnt/β-catenin signaling pathway 3. The protein interacts with zonula occludens-1 (ZO-1) and is targeted by CAF-derived exosomal miR-29b-1-5p in gastric cancer progression 4. VSIG1 also shows clinical significance in hepatocellular carcinoma, where co-expression with TTF-1 characterizes gastric-type HCC with better prognosis 56.