Neuropeptides are regulators of synaptic transmission and their effects are mediated by G-protein coupled receptors. NPS (Neuropeptide S) is a 20 amino acid peptide cleaved from a larger precursor that contains a hydrophobic signal peptide and proteolytic cleavage processing sites. The N-terminal residue of NPS is always a serine regardless of the species. NPS is predominantly found in the central nervous system and plays an important role regulating sleep/wake functions, locomotion, arousal/anxiety responses and food intake. NPS functions by binding and activating its receptor, NPSR, and increasing intracellular calcium levels thereby acting as an excitatory transmitter. In addition, NPS stimulates the hypothalamo-pituitary adrenal (HPA) axis via the release of corticotropin-releasing factor (CRF) and arginine vasopressin (AVP). NPS and its receptor NPSR may also play a role in asthma pathogenesis.