HTR3D encodes a subunit of the 5-hydroxytryptamine type-3 (5-HT3) receptor, a serotonin-gated cation-selective ion channel belonging to the Cys-loop superfamily 1. This subunit forms pentameric channel complexes with other HTR3 family members (HTR3A, HTR3B, HTR3C, HTR3E), mediating fast neuronal depolarization upon serotonin activation 1. HTR3D expression is restricted to kidney, colon, and liver tissues, distinguishing it from more broadly distributed HTR3 subunits 2. The channel's conductance properties depend on the intracellular amphipathic helix domain, with HTR3D composition influencing single-channel conductance characteristics 3. Clinically, HTR3D variants associate with multiple conditions. A nonsynonymous variant (p.G36A, rs6443930) correlates with differential chemotherapy-induced nausea and vomiting susceptibility 4. Additionally, HTR3D polymorphisms contribute to childhood acute lymphoblastic leukemia (ALL) susceptibility, with the rs6779545 A allele increasing ALL risk and elevating HTR3D mRNA expression 5. HTR3D variants also show mild associations with primary angle-closure glaucoma in Chinese populations 6. These findings suggest HTR3D genetic variation modulates serotonin signaling relevant to gastrointestinal, hematologic, and ophthalmologic conditions.