Claudin 5（ CLDN5） is a key structural component of intercellular tight junction proteins and has been identified as one of the most important intercellular tight junction proteins in the blood-cerebrospinal fluid barrier. Numerous studies have demonstrated that blood-cerebrospinal fluid barrier dysfunction is an important mechanism in the occurrence and progression of depressive disorder. CLDN5， one of the most important intercellular tight junction proteins in the blood-cerebrospinal fluid barrier， has also received much attention. This paper reviews the relationship between CLDN5 gene and the occurrence and treatment of depressive disorder， aiming to provide a reference for future research.