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By Charlotte O'Donnell PhD The genes of the IL-36 family members are located in a cluster on chromosome 2 [1]. All three activating ligands, IL-36α, IL-36β and IL-36γ share the classic IL-1 β-trefoil structure, and lack a signal peptide. IL-36α, IL-36β, and IL-36γ lack a signal sequence, and thus cannot be transported to the endoplasmic reticulum. Similar to IL-1β and IL-18, the N-terminus must be cleaved for full agonist or antagonist bioactivity of each of the IL-36 cytokines. The protease responsible for this cleavage has not yet been elucidated. It is not thought to be a caspase as the site does not resemble a caspase cleavage site [2]. These th …