CLDN7 (claudin 7) is a tight junction protein that plays a critical role in maintaining intercellular adhesion and epithelial barrier integrity. As a core component of tight junctions, CLDN7 functions to obliterate intercellular space and mediate calcium-independent cell-cell adhesion 1. In normal physiology, CLDN7 expression is upregulated through histone crotonylation-dependent transcriptional mechanisms to fortify intestinal epithelial barriers 2, and its expression is essential for decidual macrophage adhesion and retention during pregnancy 3. In cancer contexts, CLDN7 functions as a tumor suppressor. In breast cancer, CLDN7 overexpression suppresses invasion and metastasis by repressing smooth muscle actin-related genes and mesenchymal phenotype programs 4. Similarly, CLDN7 is significantly overexpressed in breast cancer tissues but associates with poor disease-free survival, with elevated expression correlating with altered immune cell activation patterns 5. In renal cell carcinoma, CLDN7 downregulation via promoter hypermethylation promotes tumor progression, EMT, and poor prognosis 6. Conversely, in colorectal cancer, CLDN7 deficiency drives immunosuppression by recruiting neutrophils and inducing their metabolic reprogramming toward pro-tumor phenotypes via NF-κB/CXCL1 signaling 7. CLDN7 is aberrantly expressed across multiple hepatocellular carcinoma contexts 1, and identified as a key epithelial marker in ovarian endometriomas 8. These findings establish CLDN7 as both a barrier function regulator and a context-dependent modulator of cancer progression and immune homeostasis.