{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTAS2R38 is a prototypical bitter taste receptor that underlies the ability to perceive compounds such as phenylthiocarbamide (PTC) and 6‐n‐propylthiouracil (PROP). Early genetic studies identified a small region on chromosome 7 encompassing the TAS2R38 gene, and three coding single‐nucleotide polymorphisms generate haplotypes—most notably the “taster” (PAV) and “nontaster” (AVI) forms—that explain a large proportion of the variance in bitter taste sensitivity. These genetic variants not only account for the classic bimodal distribution of taste sensitivity but also show a complex pattern of inheritance that has been maintained by balancing natural selection. Studies in both children and adults have further linked these allelic differences with variability in taste thresholds, perceived bitterness intensity, and even gustatory developmental factors."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical role in bitter taste perception, TAS2R38 is expressed in extraoral tissues where it contributes to innate immune defense and other non‐gustatory functions. In the human upper airway epithelium, for example, TAS2R38 is activated by bacterial quorum-sensing molecules that trigger calcium‐dependent nitric oxide production, leading to enhanced mucociliary clearance and direct antibacterial effects. Moreover, the receptor is found on lymphocytes and other immune cells where its activation modulates cellular responses, and in gastrointestinal L-cells where stimulation of TAS2R38 can induce the release of glucagon-like peptide-1. Intriguingly, TAS2R38 expression has also been documented in tumor cells, suggesting potential links between microbial signaling, taste receptor function, and carcinogenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "21"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic variation in TAS2R38 has been associated with broader clinical and behavioral outcomes. Variants of this receptor not only influence dietary preferences, food acceptance, and sweetness perception through their effects on bitter sensation but have also been linked to markers of adiposity, dental caries risk, and even tobacco dependence. In addition, the TAS2R38 genotype appears to correlate with chronic rhinosinusitis severity and surgical outcomes, while emerging evidence suggests associations with susceptibility to certain cancers such as gastric malignancy. Structural and computational modeling studies have provided insights into ligand binding, offering mechanistic explanations for the functional differences between receptor variants. Collectively, these findings illustrate a multifaceted role for TAS2R38 that spans from peripheral taste transduction to immune surveillance and systemic metabolic regulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "22", "end_ref": "39"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Un-kyung Kim, Eric Jorgenson, Hilary Coon, et al. 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