IL-6R alpha (IL-6RA) is a subunit alpha of IL-6 receptors, also shared by other interleukin receptors. IL-6RA is a type I transmembrane glycoprotein, which forms a complex with the type I transmembrane signal transducer Glycoprotein 130 (CD130) and regulates the biological activity of IL-6 with a low affinity. IL-6RA acts as IL-6 agonist and involves in JAK/STAT, MAPK, and Akt signaling pathway. IL-6RA has 2 isoform including mIL-6R (the longer one) or sIL-6R (the shorter one): The mIL-6R is membrane-bound interleukin-6 receptor, has the potential to drive naive CD4+ T cells to the Th17 lineage, through ‘cluster signaling’ by dendritic cells. The sIL-6R is soluble interleukin-6 receptor subunit, cleaved from IL-6RA in activated CD4+ T cells by proteolysis, and serves as IL-6 agonist. sIL-6R binds membrane-bound IL-6R and subunit IL6ST to activate regenerative and anti-inflammatory signal via IL-6 trans signaling and promotes pro-inflammatory properties of IL-6. The hydrolysis of IL-6R alpha is also called ectodomain shedding. IL-6RA involves in regulating cell growth and differentiation, and plays an important role in regulation of immune response, acute-phase reactions and hematopoiesis. However, IL-6RA shows tissue expression specificity in liver and some cells of the immune system, thus results a limitation of IL6 signaling. It’s worth noting that IL-6RA dysregulation is implicated in the pathogenesis of many diseases, such as multiple myeloma, autoimmune diseases, and prostate cancer.