HTR3E encodes the serotonin receptor 3E subunit, which forms serotonin-activated cation-selective ion channels in the Cys-loop superfamily 1. The gene is clustered with HTR3C and HTR3D on chromosome 3 and shows restricted expression predominantly in the colon and intestine 2. During human intestinal development, HTR3E is specifically associated with tuft cells throughout gestation and adulthood, suggesting roles in intestinal development 3. HTR3E functions as part of heteropentameric or homomeric ion channel complexes that mediate fast neuronal depolarization and regulate gastrointestinal motility and secretion 1. The receptor's intracellular amphipathic helix domain contributes to ion permeation and single-channel conductance 4. Clinically, HTR3E variants are significant disease biomarkers. The c.*76G>A variant (rs56109847) is a risk factor specifically for female diarrhea-predominant irritable bowel syndrome (IBS-D) 567. This polymorphism disrupts microRNA-510 binding in the 3'-UTR, leading to HTR3E overexpression and increased IBS-D risk 7. Additionally, HTR3E is among five neurotransmitter receptor genes identified as potential biomarkers for Alzheimer's disease, showing altered expression and associations with immune infiltration patterns 8.