In addition, CLDNs frequently show aberrant expression and/or localization in a wide variety of cancers, resulting in either promotion or repression of tumor progression, most probably by dysregulated CLDN signaling.19–25, 22,26–32 Moreover, recent studies have established the region-selective CLDN5 breakdown in brain disorders, such as schizophrenia, depression, Alzheimer’s disease, and multiple sclerosis.33–39 In this respect, we and others have previously reported how endothelial CLDN5 expression is regionally disrupted in these psychiatric disorders.40,41. This evidence concerns the gene CLDN5 and early-onset autosomal dominant Alzheimer disease.