IL-17D is a pro-inflammatory cytokine member of the IL-17 family that functions as a pleiotropic immune mediator with tissue-specific effects. Structurally, IL-17D exhibits protein homodimerization activity and receptor ligand activity, operating through CD93 as a functional receptor on endothelial cells 1. Primary function: IL-17D induces expression of inflammatory cytokines IL-6, IL-8, and GM-CSF from endothelial cells, contributing to immune cell recruitment and activation 2. Mechanism: IL-17D signals through CD93 to activate CD8+ T-cell suppressive macrophage polarization via the CAMKII/NF-κB pathway 3, and promotes endothelial ferroptosis through miR-181a-5p/SLC7A11 signaling, elevating reactive oxygen species and inflammatory mediators 1. Disease relevance: IL-17D is implicated in multiple pathologies including psoriasis, spondyloarthritis, atherosclerosis, and gestational diabetes mellitus 2415. In atherosclerosis, IL-17D elevation correlates with increased major adverse cardiovascular events 1. In cancer, IL-17D promotes immune evasion and resistance to anti-PD-1 immunotherapy in liver metastasis 3. Clinical significance: The IL-17 family represents a major therapeutic target, with multiple FDA-approved agents targeting IL-17A, though IL-17D's distinct functions warrant specific investigation for comprehensive pathway inhibition 6.