NPSR1 encodes neuropeptide S receptor 1, a G-protein coupled receptor that binds neuropeptide S (NPS) and activates multiple signaling pathways 1. Upon NPS binding, NPSR1 initiates Gq/GNAQ-dependent phospholipase C activation, resulting in calcium mobilization from intracellular stores, and simultaneously activates cAMP/PKA signaling pathways 21. Both pathways converge to activate ERK1/ERK2 phosphorylation cascades 3. NPSR1 plays significant roles in anxiety-related behaviors and inflammatory processes. A functional polymorphism (Asn107Ile, rs324981) influences personality traits, impulsivity, ADHD symptoms, and response inhibition, with T-allele carriers showing enhanced error monitoring and anxiety sensitivity 45. In disease contexts, NPSR1 variants are associated with generalized anxiety disorder and asthma-related anxiety 67. NPSR1 also contributes to inflammatory conditions, with elevated expression in endometriosis and inflammatory bowel disease 89. In these conditions, NPSR1 activation promotes pro-inflammatory cytokine release and immune cell recruitment. NPSR1 antagonists show therapeutic potential by reducing inflammation and pain in experimental models while avoiding CNS effects when peripherally restricted 10.