Interleukins (IL) are immunomodulatory proteins that elicit a wide array of responses in cells and tissues. Interleukin 37 (IL-37, IL-1 F7) is a member of the IL-1 family. There are five isoforms of IL-37 (a-e) of which transcript IL-37b is known to be functional (Sharma et al. 2008). This isoform is represented in UniProt as the canonical form of IL-37 and in Reactome as the full length, unprocessed form of IL-37. Like several other IL-1 family members, IL-37 is synthesized as a precursor that requires processing (primarily by caspase 1) to attain full receptor agonist or antagonist function. The putative caspase 1 cleavage site is at aspartic acid 20 (Kumar et al. 2002). However, other truncation sites in IL-37 have been suggested (Pan et al. 2001). Once processed, Caspase 1 dissociates from the protein. Caspase 1 may not be the only enzyme responsible for IL-37 processing (Sharma et al. 2008). These events ultimately lead to suppression of cytokine production in several types of immune cells resulting in reduced inflammation. This is a black box event because the cleavage sites and the enzymes responsible for the processing of IL-37 are uncertain.