CRHR1 (corticotropin-releasing hormone receptor 1) is a G-protein coupled receptor that binds corticotropin-releasing hormone (CRH) and activates adenylyl cyclase signaling, leading to increased intracellular cAMP levels 1. The receptor plays a crucial role in the hypothalamic-pituitary-adrenal (HPA) axis and extrahypothalamic stress responses, where it acts as a neuromodulator organizing behavioral and humoral stress reactions 1. CRHR1 signaling involves cAMP/Ras/MAPK pathways and can impair mitochondrial function in colonocytes during stress responses 2. The receptor is significantly involved in psychiatric conditions, with genetic variants (rs242941, rs1876828, rs242939) associated with increased depression risk 3. CRHR1 also mediates pain-related anxiodepression through hippocampus-to-prefrontal cortex circuits, where CRH+ neurons activate CRHR1 to cause feed-forward inhibition 4. Additionally, CRHR1 contributes to stress-induced gut dysbiosis by damaging mitochondria and causing epithelial hypoxia 2. The receptor has therapeutic relevance in multiple contexts, including asthma treatment response 5 and interaction with childhood trauma in suicide risk 6, making it an important target for stress-related disorders.