RXFP3 (relaxin family peptide receptor 3) is a G protein-coupled receptor that primarily binds relaxin-3, a neuropeptide abundantly expressed in GABAergic neurons with well-conserved distribution across species 1. The receptor couples to Gi/o proteins and inhibits cAMP accumulation upon ligand binding 2. RXFP3 is widely distributed throughout the forebrain, including the hypothalamus, hippocampus, and prefrontal cortex, where it modulates multiple physiological processes 1. The relaxin-3/RXFP3 signaling system plays critical roles in stress responses, anxiety-related behaviors, feeding and metabolism, arousal, motivation and reward, circadian rhythms, and learning and memory 13. Electrophysiological studies demonstrate that RXFP3 agonists can directly hyperpolarize thalamic neurons 1. Recent structural studies reveal that relaxin-3 can activate both RXFP3 and RXFP4, with the C-terminal residues of relaxin-3's B chain making extensive contacts with conserved receptor residues 4. The system shows therapeutic potential for treating neuropsychiatric disorders including anxiety, depression, obesity, and alcohol addiction 56. RXFP3 has also been detected in human spermatozoa, suggesting additional reproductive functions 7.