Interleukin-6 (IL6) is a pleiotropic cytokine that has important roles in immunity and inflammation and in some cancers. It can have both pro- and anti-inflammatory activities. Blockade of IL-6 signalling is used to treat both rheumatoid arthritis and Castleman’s Disease. In order to signal, IL6 binds to a specific receptor (IL6-R) found on the surface of target cells. Recently, we have identified a novel protein that controls the levels of this receptor found expressed on the cell surface. This project aims to understand the molecular basis of IL-6 receptor down-regulation and the biological consequences on the immune system. Since the centrality of IL6 to several human diseases has been demonstrated by the approval of IL6 inhibitors for clinical use, understanding the mechanism of inhibition by this novel family of IL6 inhibitors may point to new therapeutic approaches to treating these diseases.