FK506-binding protein 5 (FKBP5) is a 51 kDa immunoaffinity protein encoded by the FKBP5 gene. It is a key negative regulator in the glucocorticoid receptor signaling pathway, and plays a core regulatory role in the physiological and pathological processes of the stress response. As a molecular chaperone for numerous proteins, FKBP5 not only regulates the functions of target proteins in cells but also exerts regulatory effects on expression at the transcriptional, post-transcriptional, and post-translational levels. Therefore, FKBP5 is the core regulatory hub of the body's stress response system. It directly affects the homeostasis of the hypothalamic-pituitary-adrenal axis by negatively regulating the glucocorticoid receptor signaling pathway, thereby integrating genetic susceptibility, environmental stress, and epigenetic changes into sustained pathophysiological responses. This unique "integrator" role makes FKBP5 a key molecular target for understanding and intervening in various stress-related neuropsychiatric disorders. Numerous studies have shown that FKBP5 plays an important role in neuropsychiatric diseases such as depression, post-traumatic stress disorder, and anxiety disorder. This article reviews the research progress on the protein structure and molecular function, expression regulation, and role in neuropsychiatric diseases of FKBP5. By gaining a deeper understanding of the role of FKBP5 molecules in neuropsychiatric diseases, it is expected to provide new targets and ideas for the treatment of related diseases.

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