The key molecules playing potential roles in the pathogenesis of acute and chronic itch in inflammatory skin diseases are endothelin-1 (ET-1), interleukin 31 (IL-31), interleukin 6 (IL-6), interleukin 17 (IL-17), interleukin 33 (IL-33), tumor necrosis factor α (TNF-α), thymic stromal lymphopoietin (TSLP), and peroxisome proliferator activator γ (PPAR-γ) that can activate directly or indirectly pruritic nerve endings. The gene discussed is EDN1; the disease is inflammatory skin disease.