IL17RE (interleukin 17 receptor E) is a specific functional receptor for IL-17C that mediates innate immune responses to bacterial pathogens 1. The receptor signals through NF-κB and MAPK pathways, requiring the adaptor protein TRAF3IP2/ACT1 for signal transduction 2. IL17RE represents one member of the IL-17 receptor family (IL-17RA to IL-17RE), which shares unique structural features distinguishing it from other cytokine receptor families 3. Alternative splicing generates functionally distinct isoforms: isoforms 2 and 4 function as either cytoplasmic inactive or dominant-active signaling forms, while isoforms 3 and 5 act as soluble decoy receptors [UniProt annotation]. IL-17 signaling through IL-17R family members promotes Th17 cell-mediated immunity and protects against extracellular pathogens, but also drives chr3 inflammation in autoimmune diseases including rheumatoid arthritis, psoriasis, and multiple sclerosis 4. The receptor mediates autonomous signaling through Act1-SHP2 complexes, sustaining inflammation even during anti-IL-17 therapy 5. Therapeutically, IL-17 receptor inhibition via brodalumab has demonstrated efficacy in treating psoriasis and other immune-mediated inflammatory diseases 6, though paradoxical adverse cutaneous reactions occasionally occur 7.