In 1997, caspase-12 was cloned from a murine L929r2 fibrosarcoma cDNA library. 1 As depicted in Figure 1a, the caspase-12 gene is located on chromosome 9. The genes for caspase-1 and-11, the closest phylogenetic relatives of caspase-12, reside upstream (50) of the caspase-12 gene, while the genes for the D polypeptide of platelet-derived growth factor (PDGF-D) and for two members of the large matrix metalloprotease (MMP) family, that is, MMP-13 and-12, are localized downstream (30) of caspase-12. The caspase-12 gene itself consists of 11 exons (Figure 1a). The entire N-terminal CARD is encoded by exons 1 and 2. The CARD is separated from the large catalytic subunit by a small linker region, encoded by the relatively small exons 3–5. The large and small catalytic subunits of caspase-12 arise from exons 5–8 and 8–10, respectively. The end of exon 10 also contains a small part of the 30-untranslated region (30UTR), while the remainder of the 30UTR is encoded by exon 11 (Figure 1a). The mRNA of this caspase (Genbank accession code Y13090) encodes a protein of 48kDa. 1 Based on primary sequence homology, caspase-12 can be classified as an inflammatory caspase, since it shares the highest aminoacid sequence identity with murine caspase-1 and-11 and human caspase-1,-4 and-5 (Table 1 and Figure 1c). 1