This study investigates the complex phenotype of mice lacking occludin, a component of tight junctions (TJs). Occludin−/− mice, generated by disrupting the occludin gene, showed significant postnatal growth retardation and normal morphology and barrier function of TJs in the intestinal epithelium. However, they exhibited histological abnormalities in several tissues, including chronic inflammation and hyperplasia of the gastric epithelium, calcification in the brain, testicular atrophy, loss of cytoplasmic granules in striated duct cells of the salivary gland, and thinning of the compact bone. These findings suggest that the functions of TJs and occludin are more complex than previously thought. The study also highlights the need for further detailed analyses to understand the molecular mechanisms behind the complex phenotypes of occludin−/− mice.This study investigates the complex phenotype of mice lacking occludin, a component of tight junctions (TJs). Occludin−/− mice, generated by disrupting the occludin gene, showed significant postnatal growth retardation and normal morphology and barrier function of TJs in the intestinal epithelium. However, they exhibited histological abnormalities in several tissues, including chronic inflammation and hyperplasia of the gastric epithelium, calcification in the brain, testicular atrophy, loss of cytoplasmic granules in striated duct cells of the salivary gland, and thinning of the compact bone. These findings suggest that the functions of TJs and occludin are more complex than previously thought. The study also highlights the need for further detailed analyses to understand the molecular mechanisms behind the complex phenotypes of occludin−/− mice.