SLC6A4 encodes the serotonin transporter (SERT), which mediates serotonin reuptake from the synaptic cleft through cotransport with sodium and chloride ions in exchange for potassium 123456. This transporter is essential for serotonin homeostasis in the central nervous system and regulates serotonin levels across multiple physiological systems, including the gastrointestinal tract and blood platelets. In developing cortex, SERT controls serotonin uptake in glutamatergic neurons to organize sensory circuits, while in mature brain it primarily functions in raphe neurons to terminate synaptic serotonin signaling. The transport mechanism involves conformational cycling from outward-open to inward-open states, with Na+ and Cl- remaining bound throughout the cycle 123456. SLC6A4 gene variants significantly influence serotonin transport capacity, with combinations of polymorphisms capable of producing up to 40-fold differences in vitro 7. The 5-HTTLPR promoter polymorphism is extensively studied for associations with anxiety-related traits and psychiatric disorders. SLC6A4 short alleles moderate the effects of childhood adversity on adolescent mental health; notably, the short/short genotype amplified anxiety risk in children exposed to food insecurity 8. However, meta-analyses show no definitive associations between SLC6A4 variants and temporal lobe epilepsy susceptibility or pulmonary arterial hypertension 910, and associations with sensory processing sensitivity remain unconfirmed 11.