IL17RD (interleukin 17 receptor D) is a transmembrane feedback inhibitor that negatively regulates multiple signaling pathways critical for development and immune homeostasis 1. Its primary function involves suppressing fibroblast growth factor (FGF)-mediated Ras-MAPK signaling by spatially blocking nuclear translocation of activated ERK without inhibiting cytoplasmic phosphorylation 23. IL17RD also regulates interleukin-17A and Toll-like receptor signaling pathways 1, and inhibits TGF-β-induced epithelial-to-mesenchymal transition in lens epithelial cells. Clinically, IL17RD mutations cause congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS), typically acting as oligogenic contributors alongside other FGF pathway variants 4. Notably, IL17RD mutations in KS patients are strongly linked to hearing loss (75% of carriers) 4. In a large Chinese cohort, IL17RD variants required additional genetic hits for disease manifestation, suggesting synergistic inheritance patterns 5. Beyond reproductive disorders, elevated IL17RD expression serves as an independent favorable prognostic biomarker in glioblastoma, correlating with improved overall survival 6. In triple-negative breast cancer, IL17RD acts as a tumor suppressor, and its epigenetic upregulation by thymoquinone reduces cancer cell growth and metastasis 7. Recent evidence indicates IL17RD mediates IL17A-dependent myeloid cell infiltration in aortic inflammation 8 and associates with fixed airflow obstruction in asthma-COPD overlap 9.