CLDN18 (claudin-18) is a tight junction protein essential for gastric epithelial barrier function. The CLDN18.2 isoform is normally expressed exclusively in differentiated gastric mucosa cells 1, where it mediates calcium-independent cell-cell adhesion and participates in tight junction assembly to maintain the gastric paracellular barrier against acidification. During malignant transformation, CLDN18.2 becomes aberrantly accessible on tumor cell surfaces 2, making it an attractive therapeutic target. CLDN18.2 expression is retained in gastric and gastroesophageal junction adenocarcinomas, with frequent ectopic activation also occurring in pancreatic, esophageal, ovarian, and lung cancers 1. Clinically, CLDN18.2 represents a druggable biomarker for advanced gastric cancer. The monoclonal antibody zolbetuximab targeting CLDN18.2, combined with chemotherapy, significantly prolonged progression-free and overall survival in CLDN18.2-positive, HER2-negative patients compared to chemotherapy alone in phase 3 trials (GLOW and SPOTLIGHT), with median overall survival improvements of 2-3 months 34. Emerging therapies include CAR-T cells targeting CLDN18.2, demonstrating an overall response rate of 38.8% with manageable safety profiles 5. These advances have substantially expanded targeted therapy options for gastric cancer patients, with CLDN18.2 testing via immunohistochemistry (≥75% moderate-to-strong membrane staining) now recommended for clinical practice 6.