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One of the most critical components of the stress response system is the hypothalamus-pituitary-adrenal (HPA) axis. The FKBP prolyl isomerase 51 (FKBP51) protein is one of the main negative regulators of the HPA axis. FKBP51 negatively regulates the cortisol effects (the end product of the HPA axis) by inhibiting the interaction between glucocorticoid receptors (GRs) and cortisol, causing reduced transcription of downstream cortisol molecules. By regulating cortisol effects, the FKBP51 protein can indirectly regulate the sensitivity of the HPA axis to stressors. Previous studies have indicated the influence of FKBP5 gene mutations and epigenetic changes in different psychiatric diseases and drug responses and recommended the FKBP51 protein as a drug target and a biomarker for psychological disorders. In this review, we attempted to discuss the effects of the FKBP5 gene, its mutations on different psychiatric diseases, and drugs affecting the FKBP5 gene.<\/jats:p>","DOI":"10.3389\/fpsyt.2023.1182345","type":"journal-article","created":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T00:35:26Z","timestamp":1686875726000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":54,"title":["Role of FKBP5 and its genetic mutations in stress-induced psychiatric disorders: an opportunity for drug discovery"],"prefix":"10.3389","volume":"14","author":[{"given":"Mahdi","family":"Malekpour","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorsa","family":"Shekouh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Ebrahim","family":"Safavinia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shadi","family":"Shiralipour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Jalouli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar","family":"Mortezanejad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Negar","family":"Azarpira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niloofar Dehdari","family":"Ebrahimi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,6,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12958-018-0431-1","article-title":"Radiations and male fertility","volume":"16","author":"Kesari","year":"2018","journal-title":"Reprod Biol Endocrinol."},{"key":"B2","unstructured":"Global Health Data Exchange (GHDx)"},{"key":"B3","unstructured":"KovacevicR\n          Mental Health: Lessons Learned in 2020 for 2021 and Forward 2021"},{"key":"B4","doi-asserted-by":"publisher","first-page":"85","DOI":"10.26444\/aaem\/106085","article-title":"Effect of ionizing radiation on the male reproductive system","volume":"26","author":"Wdowiak","year":"2019","journal-title":"Ann Agricul Environ Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/S0193-953X(05)70283-5","article-title":"Definition and epidemiology of treatment-resistant depression","volume":"19","author":"Fava","year":"1996","journal-title":"Psychiatr Clin North Am."},{"key":"B6","doi-asserted-by":"publisher","first-page":"579566","DOI":"10.3389\/fpsyt.2021.579566","article-title":"Why psychotropic drugs don't cure mental illness-but should they?","volume":"12","author":"Ivanov","year":"2021","journal-title":"Front Psychiatry."},{"key":"B7","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/S2215-0366(21)00395-3","article-title":"Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990\u20132019: a systematic analysis for the Global Burden of Disease Study 2019","volume":"9","author":"Collaborators","year":"2022","journal-title":"Lancet Psychiatry."},{"key":"B8","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1111\/acps.13459","article-title":"Symptomatic versus disease-modifying effects of psychiatric drugs","volume":"146","author":"Ghaemi","year":"2022","journal-title":"Acta Psychiatr Scand."},{"key":"B9","doi-asserted-by":"publisher","first-page":"150","DOI":"10.36131\/cnfioritieditore20220303","article-title":"Etiology of psychiatric disorders: lay beliefs and the role of gender, field of study and personality traits","volume":"19","author":"Troisi","year":"2022","journal-title":"Clin Neuropsychiatry."},{"key":"B10","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1097\/01213011-200502000-00001","article-title":"Pharmacogenetics in the treatment of depression: pharmacodynamic studies","volume":"15","author":"Serretti","year":"2005","journal-title":"Pharmacogenet Genom."},{"key":"B11","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1002\/wps.20436","article-title":"Etiology in psychiatry: embracing the reality of poly-gene-environmental causation of mental illness","volume":"16","author":"Uher","year":"2017","journal-title":"World Psychiatry."},{"key":"B12","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1177\/0269881115576688","article-title":"Treatment resistant or resistant to treatment? 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