Claudin-4 is one of twenty-seven integral membrane tight junction proteins and specializes in paracellular sodium transport. Although claudin proteins are primarily known for their cell adhesion function, Claudin-4 binds to zonula occludens proteins and interacts with numerous signaling pathways.

Claudin-4 is detectable in low amounts in the normal tissues of the lung, kidney, breast, prostate, bladder and gastrointestinal tract. It is a highly specific and sensitive membranous marker for most epithelial neoplasms.  Absence of expression in normal mesothelium and mesothelioma provides utility in the differential diagnosis between carcinoma from mesothelioma with 99% specificity.  In breast tumors, claudin-4 levels are significantly higher in ER-negative and high grade tumors when compared to ER-positive and low grade tumors. High levels of Claudin-4 expression are associated with later stages of progression and reduced patient survival for most types of epithelial neoplasms.   Conversely, its expression is downregulated in gastric and high-grade bladder cancers, and is significantly lower in lymph node metastasis and esophageal tumors with distant metastasis. Low Claudin-4 expression is associated with a poor prognosis in esophageal squamous cell carcinoma.