Relaxin-3 (RLN3) is a neuropeptide highly expressed in the nucleus incertus (NI), a pontine brain region conserved across species from teleosts to primates 1. RLN3 functions as a ligand for G protein-coupled receptors RXFP3 and RXFP4, mediating neuropeptide signaling in the central nervous system 2. Central RLN3 administration increases food intake and adiposity, with polymorphisms associated with obesity and hypercholesterolemia in humans 3. RLN3 exhibits pronounced sex-specific effects: females demonstrate higher sensitivity to RLN3's orexigenic effects, and stress-induced binge eating in females is blocked by RXFP3 antagonists 3. The RLN3/RXFP3 system is modulated by estrogen across the estrous cycle, implicating involvement in feeding behavior fluctuations 4. RLN3 neurons project extensively throughout the brain including the hippocampus, septum, and hypothalamus, supporting roles in arousal, learning, memory, and stress responses 1. In fish models, RLN3 is essential for spermatogenesis and male fertility through androgen production via the hypothalamic-pituitary-gonadal axis 5. Recent evidence suggests RLN3 involvement in neurodegenerative pathology, with phosphorylated-tau accumulation in NI neurons of Alzheimer's disease subjects 6.