HTR3B encodes the B subunit of the serotonin 5-HT3 receptor, a pentameric ligand-gated ion channel that forms serotonin-activated cation-selective channels 1. Upon serotonin binding, HTR3B-containing receptors mediate fast, depolarizing neuronal responses through calcium and monoatomic ion transport. The gene exhibits tissue-specific alternative promoters, with distinct transcription start sites in brain versus intestinal tissues, generating functionally different 5-HT3B isoforms 1. Naturally occurring HTR3B variants significantly alter receptor properties; variants p.Y129S and p.S156R increase maximum serotonin responses, while p.V183I reduces surface expression of heteromeric 5-HT3A/B receptors 2. HTR3B polymorphisms show robust clinical associations: the rs1176744 A allele associates with increased depression risk and executive dysfunction in Chinese populations 3, while rs3782025 correlates with alcoholism comorbid with antisocial behavior and reduced alpha EEG power 4. The rs3758987 polymorphism predicts post-operative vomiting 5 and motion sickness-induced vomiting susceptibility 6. These associations reflect HTR3B's role in serotonergic regulation of mood, behavior, and nausea pathways, positioning the receptor as a potential therapeutic target for psychiatric and gastrointestinal disorders.