HTR5A encodes a G-protein coupled receptor for serotonin (5-hydroxytryptamine) and ergot alkaloid derivatives 123. The receptor is coupled to G(i)/G(o) alpha proteins and mediates inhibitory neurotransmission by suppressing adenylate cyclase activity and activating phosphatidylinositol-calcium second messenger systems that regulate intracellular calcium release 123. HTR5A plays roles in multiple neuropsychiatric conditions. Genetic variants in HTR5A are associated with schizophrenia susceptibility and impaired executive function; specifically, rs1800883 showed significant associations with schizophrenia in both discovery and replication cohorts and interacted with perseverative errors on cognitive testing 4. HTR5A variants also contribute to mood disorder etiology through main genetic effects independent of childhood adversity 5. Beyond neuropsychiatry, cortisol upregulates HTR5A expression in adipocytes and macrophages, where it mediates stress-enhanced adipogenesis and metabolic dysfunction 6. HTR5A expression increases in pyramidal neurons in response to increased intracranial pressure, suggesting neuroprotective involvement 7. Placental HTR5A expression patterns are associated with early infant neurodevelopmental outcomes, highlighting serotonergic signaling importance in fetal brain development 8. However, HTR5A polymorphisms did not predict antidepressant treatment response in major depression 9.