CLDN6 (claudin 6) is a tight junction protein that functions as both a tumor suppressor and therapeutic target in cancer. As a member of the claudin family, CLDN6 normally participates in cell-cell adhesion and tight junction assembly 1. In breast cancer, CLDN6 acts as a tumor suppressor by inhibiting growth and metastasis through regulation of fatty acid metabolism, specifically by preventing RAS palmitoylation via the MAGI2/KLF5/SREBP1 pathway 1. However, CLDN6 exhibits oncofetal antigen properties, being absent from normal adult tissues but aberrantly upregulated in various malignancies including ovarian, endometrial, and germ cell tumors 234. This tumor-specific expression pattern makes CLDN6 an attractive therapeutic target. Multiple CLDN6-directed therapies are under clinical investigation, including antibody-drug conjugates (ADCs), T-cell engagers, CAR-T cells, and RNA-encoded bispecific antibodies 56274. Clinical trials have demonstrated promising efficacy, with objective response rates of 28-60% for CLDN6-targeted ADCs and 33% for CLDN6 CAR-T cells in solid tumors 84. The dual nature of CLDN6 as both tumor suppressor and therapeutic target highlights its complex role in cancer biology.