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Interleukin-17 receptor D (IL-17RD), also known as SEF (Similar Expression to FGF genes), is a single-pass type I transmembrane protein and a member of the IL-17 receptor family [UniProt: Q8NFM7]. It is distinct for its dual functionality, acting as both a modulator of interleukin-17 (IL-17) cytokine signaling and a potent feedback inhibitor of fibroblast growth factor (FGF) signaling [NCBI Gene: 54756]. By forming heterodimers with IL-17RA, IL-17RD participates in the pro-inflammatory signaling pathways triggered by IL-17A, which are central to the pathogenesis of autoimmune diseases like psoriasis [Mellett et al., 2012, PubMed: 21844396]. Simultaneously, it regulates cell proliferation and differentiation by sequestering components of the Ras/MAPK pathway, often acting as a tumor suppressor in various malignancies [UniProt: Q8NFM7]. Mutations in the IL17RD gene have been linked to Kallmann syndrome, a form of hypogonadotropic hypogonadism, highlighting its importance in developmental biology [Miraoui et al., 2013, PubMed: 23542697]. While there are currently no FDA-approved drugs that specifically target IL-17RD, its role in coordinating immune and growth factor pathways makes it a target of interest for treating chronic inflammatory disorders and certain cancers.
Modulation of IL-17 signaling through heterodimerization with IL-17RA and inhibition of FGF-mediated Ras/MAPK signaling pathways.
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