{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ILDR1, also known as angulin‐2, is a conserved transmembrane receptor that plays dual roles in epithelial cell biology. In several studies of tricellular tight junctions (tTJs), ILDR1 has been shown to localize at the vertices where three cells meet and to recruit tricellulin, thereby contributing to the integrity of the paracellular barrier. This function is especially critical in the inner ear, where proper tTJ assembly is essential for maintaining the ionic and molecular environment required for auditory transduction. Indeed, multiple independent genetic investigations have identified loss‐of‐function mutations in ILDR1 as causative for nonsyndromic sensorineural hearing loss (DFNB42) in diverse populations, with animal models and cellular experiments further demonstrating that ILDR1 dysfunction leads to mislocalization of tricellulin and subsequent degeneration of cochlear hair cells and associated neurosensory structures."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": " In addition to its role in the auditory system, ILDR1 has been implicated in gastrointestinal endocrine signaling; it is expressed exclusively in cholecystokinin‐producing cells, where it mediates the secretion of CCK in response to a specific combination of ingested fatty acids and lipoproteins."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Furthermore, studies in zebrafish have demonstrated that attenuation of ILDR1 expression disrupts inner ear development and lateral line neuromast formation, providing in vivo evidence of its critical function in sensory organ development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Collectively, these findings highlight the pleiotropic functions of ILDR1 in maintaining epithelial barrier integrity at tTJs (thereby ensuring proper auditory function) and in coupling dietary fat absorption to hormonal responses, establishing ILDR1 as a key regulator of both sensory and metabolic homeostasis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tomohito Higashi, Shinsaku Tokuda, Shin-ichiro Kitajiri, et al. 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