AVPR1B (arginine vasopressin receptor 1B) is a G protein-coupled receptor primarily expressed in pituitary corticotropes that mediates arginine vasopressin (AVP) stimulation of ACTH release, thereby regulating the hypothalamic-pituitary-adrenal (HPA) axis under stress 1. The receptor activates phospholipase C signaling, increasing cytosolic calcium and inositol phosphate biosynthesis, while also promoting vasoconstriction and regulating blood pressure 2. Clinically, AVPR1B agonists function as vasopressors in critically ill patients with vasodilatory shock, though they have not significantly reduced mortality compared to standard agents like norepinephrine 3. Genetic variation in AVPR1B contributes to psychiatric vulnerability. Multiple polymorphisms associate with childhood-onset mood disorders, particularly in females, with the Lys65Asn variant showing strongest association 1. AVPR1B variants also correlate with bipolar disorder psychotic features and influence prosocial behavior in gene-environment and gene-gene interactions with clock genes 45. The gene has undergone natural selection in human populations, with evidence of balancing selection in African and European populations, suggesting adaptive significance potentially related to mood regulation 6. AVPR1B antagonists demonstrate antidepressant properties, implicating this receptor in HPA axis dysregulation underlying mood pathology.