Caspase-1 was first described in 1989 as the cysteine proteinase responsible for the production of interleukin 1-beta (IL-1-beta) in monocytes, hence its original name, interleukin 1–beta-converting enzyme (ICE). When it was first purified, cloned and sequenced in 1992, it was found to be unrelated to any known protein. Late in 1993, it was shown to be homologous to CED-3, the product of a gene required for programmed cell death in the nematode Caenorhabditis elegans.

The crystallographic structure of caspase-1 reported in 1994 identified the residues important for binding and catalysis, and confirmed its relationship to CED-3. To date, 12 related paralogs of human origin have been described. In 1996, a unified nomenclature was introduced for these enzymes, which uses the trivial name ‘caspase’ as a root for serial names. The ‘c’ reflects a cysteine proteinase mechanism, and ‘aspase’ relates to their ability to cleave after Asp, the most distinguishing catalytic property of this family.