IL-1R8, also known as SIGIRR or TIR8, is a trans-membrane protein belonging to the IL-1 receptor family. The human gene includes ten exons, and alternative splicing can result in different isoforms. We, herein, characterized a longer isoform of IL-1R8 containing an in-frame additional sequence between the TIR domain and the C-terminal portion of the protein. IL-1R8 Long (IL-1R8L1) mRNA was specifically expressed and regulated in distinct cell lines, in a manner similar to the classic isoform. Overexpression of IL-1R8L1 resulted in the production of a corresponding protein that showed a pattern of cell localization similar to the classic isoform. An antibody directed against an IL-1R8L1 specific peptide, detected this novel isoform in different cell lines and tissues where this protein may complement the anti-inflammatory functions of classic IL-1R8. © 2017 John Libbey Eurotext.