HTR1B encodes the 5-hydroxytryptamine receptor 1B, a G-protein coupled receptor that binds serotonin and mediates inhibitory neurotransmission through Gi/Go protein coupling and adenylate cyclase inhibition 1. The receptor regulates the release of serotonin, dopamine, and acetylcholine in the brain, affecting neural activity, pain perception, mood, and behavior 2. HTR1B also plays a role in cerebral artery vasoconstriction 3. Multiple polymorphisms in HTR1B have been identified with functional significance, particularly the -161A>T and G861C variants 4. Meta-analysis evidence supports associations between HTR1B variants and substance use disorders, including alcohol, cocaine, and heroin dependence 5. The gene shows significant associations with attention-deficit/hyperactivity disorder (ADHD), ranking among seven genes with statistically significant pooled evidence across multiple studies 6. HTR1B expression is regulated by its 3' region, which contains regulatory elements that can enhance or suppress gene expression 7. Recent research demonstrates HTR1B's role in opioid use disorder through epigenetic mechanisms, with the rs6296 polymorphism affecting both gene methylation and expression 8. Additionally, HTR1B in osteoblasts contributes to acute myeloid leukemia progression through kynurenine signaling pathways 9.