PRLR (prolactin receptor) is a transmembrane cytokine receptor that mediates prolactin signaling through the canonical JAK2/STAT5 pathway, with additional activation of AKT and MAPK pathways 1. In reproductive physiology, PRLR acts as a prosurvival factor for spermatozoa by suppressing SRC kinase activation [UniProt]. Beyond reproduction, PRLR regulates diverse processes including maternal behavior, metabolic homeostasis, and immune responses 1. PRLR dysfunction contributes to multiple pathologies: adenomyosis develops through PRLR-mediated epithelial cell survival and proliferation, with PRLR inhibition (HMI-115) showing therapeutic promise 2. Conversely, prolactin deficiency impairs microglial PRLR signaling, increasing synaptic loss and cognitive dysfunction in diabetes—effects reversed by prolactin restoration 3. In cancer, aberrant PRLR signaling promotes proliferation and chemotherapy resistance across breast, prostate, ovarian, and pancreatic cancers through JAK-STAT, AKT, and MAPK activation 45. PRLR also crosstalk with EGFR/HER2 pathways to drive endocrine therapy resistance in breast cancer 6. Additionally, PRLR gene variants associate with polycystic ovarian syndrome risk 7, and elevated prolactin levels contribute to autoimmune disease severity, particularly systemic lupus erythematosus 8. PRLR antagonists represent emerging therapeutic targets across multiple disease contexts.