The proteins belonging to the claudin family are a set of tight-junction membrane proteins that facilitate paracellular movement of molecules between neighboring epithelial cells. In healthy kidneys, claudin-4 is crucial for the paracellular reabsorption of ions. Most epithelial cells show claudin-4 expression, whereas it is not found in mesothelial cells, which makes it very helpful for identifying epithelial cancers. The immunohistochemical detection of this antigen could assist in distinguishing poorly differentiated lung adenocarcinoma from mesothelial-based lesions. Similarly, determining claudin-4 expression through IHC can be beneficial in analyzing breast and endometrial lesions.