ILDR1 (immunoglobulin-like domain containing receptor 1) is a multifunctional protein with critical roles in epithelial barrier integrity and metabolic signaling. Structurally, ILDR1 localizes to tricellular tight junctions (tTJs) where it maintains their ultrastructure and function 1. As a lipoprotein receptor, ILDR1 mediates fat-stimulated cholecystokinin (CCK) secretion in intestinal enteroendocrine cells through a mechanism requiring both fatty acids and high-density lipoprotein particles 2. Clinically, ILDR1 mutations cause autosomal recessive nonsyndromic hearing loss (DFNB42) 13. ILDR1-deficient mice exhibit early-onset severe deafness with progressive degeneration of cochlear outer hair cells and disruption of the organ of Corti, while maintaining normal endocochlear potential 4. The deafness mechanism involves tricellulin mislocalization and altered expression of proteins involved in cell adhesion and cellular homeostasis. Additionally, genome-wide association studies identified ILDR1 variants associated with age-related hearing loss (ARHL) in the general population 5. Beyond otologic disease, ILDR1 is significantly overexpressed in gastric cancer tissues and correlates with poor prognosis, suggesting potential oncologic significance 6. Together, these findings establish ILDR1 as essential for tTJ maintenance, endocrine hormone secretion, and hearing preservation.