CRHBP (corticotropin releasing hormone binding protein) is a secretory glycoprotein that functions as a negative regulator of the hypothalamic-pituitary-adrenal stress axis by binding and inactivating corticotropin-releasing hormone (CRH) 12. The protein contains 10 cysteines forming 5 tandem disulfide bridges and is encoded by a gene consisting of 7 exons located on chromosome 5 1. CRHBP plays crucial roles in various physiological processes including REM sleep regulation, where pontine Crhbp+ neurons promote REM sleep through a pontine-medullary circuit 3. In pregnancy, CRHBP regulates trophoblast invasion through the PKC signaling pathway via interaction with CRH receptor 2, with reduced expression associated with recurrent pregnancy loss 4. The protein exhibits tumor suppressor activity in hepatocellular carcinoma by reducing cyclin B2 expression and dissociating cyclin B2-CDK1 complexes, leading to G2 phase cell cycle arrest 5. CRHBP is subject to degradation through p62-mediated autophagy under nutrient starvation and hypoxic conditions 5. Clinical relevance includes associations with Parkinson's disease-related REM sleep disorders 3, stress-related heroin relapse risk 6, and schizophrenia-associated aggressive behavior 7.