Characterization of caspases from Lepidoptera and their role in apoptosis Multicellular organisms need a tightly controlled regulation of cell proliferation and of cell specialization together with a controlled cell death to maintain their integrity. A family of evolutionarily conserved proteases called caspases plays a central role in regulating apoptosis in animals. The discovery of p35 a baculovirus caspase inhibitor has led to the characterization of the first lepidopteran caspase Sf Caspase 1 from Spodoptera frugiperda. Studies on the Sf Caspase 1 mode of activation suggested that apoptosis in Lepidoptera also requires a cascade of caspase activation as demonstrated in many other species. We identified 66 sequences encoding putative caspases distributed among 27 species. Phylogenetic analyses showed that Lepidoptera possess at least 5 caspases for which we propose a unified nomenclature. According to their homology to their Drosophila counterparts and their primary structure we proposed that Lep Caspase 1 2 and 3 are effector caspases whereas Lep Caspase 5 and 6 are putative initiators. The likely function of Lep Caspase 4 remains unclear. We found that Caspase 1 and 2 have complementary expression profiles during larval development suggesting a differential regulation. Caspase 3 and 6 are upregulated upon immune challenge suggesting a role in the imd pathway. Caspase 5 is upregulated during pupation and upon induction with 20 hydroxyecdysone supporting the hypothesis of Caspase 5 playing a similar role as Dronc in developmental apoptosis in Drosophila.