Major depressive disorder (MDD) and type 2 diabetes (T2D) are two common complex multifactorial disorders that share several genetic and environmental risk factors such as hypercortisolism and related genes' risk variants within the stress response and the neuroendocrine hypothalamic-pituitary axis. Under stress, the pituitary gland releases prolactin (PRL), whose effects are pleiotropic and include mood control and insulin secretion from the beta cells.1 Variations in the prolactin receptor (PRLR) gene are associated in rodent models with stress level, depression-like behavior,2 and hepatic insulin sensitivity3 and in humans with maternal glucose homeostasis and gestational diabetes.4 Furthermore, prolonged breastfeeding has been associated with reduced incidence of T2D, potentially related to PRL action. To our knowledge, no studies are reporting PRLR as a risk gene for MDD or T2D. Therefore, we aimed to investigate if the PRLR gene encoding for the PRLR plays a role in the familial comorbidity of MDD and T2D.