Relaxin-3 systems in the brain-The first 10 years

► Relaxin-3 gene encodes a conserved neuropeptide in mammals and lower species. ► GPCR135 or RXFP3 is the native G-protein coupled receptor for relaxin-3. ► Relaxin-3 is expressed in brainstem GABA neurons that project broadly to forebrain. ► Relaxin-3 neural network is hypothesised to represent an ascending arousal system. ► Relaxin-3/RXFP3 signalling has putative roles in arousal, stress, mood and memory.