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). Mothers against decapentaplegic homolog 3 (SMAD3) binds SMAD4 and this complex modulates the transcription of several genes downstream. IL-37(? 218) can bind phosphorylated SMAD3 in A549 cells (Nold M F et al. 2010, Grimsby S et al. 2004) and may affect its function.