Abstract: Within the unique Triplo-lethal region (Tpl) of the Drosophila melanogaster genome we have found a cluster of 20 genes encoding a novel family of proteins. This family is also present in the Anopheles gambiae genome and displays remarkable synteny and sequence conservation with the Drosophila cluster. The family is also present in the sequenced genome of Drosophila pseudoobscura, and homologs have been found in Aedes aegyptii mosquitoes and the honeybee (Apis mellifera), but it is not present in the sequenced genome of any non-insect species. Phylogenetic analysis suggests that the cluster evolved prior to the divergence of Drosophila and Anopheles (250MYA) and has been highly conserved since. The ratio of synonymous to nonsynonymous substitutions and the high codon bias suggest that there has been selection on this family both for expression level and function. We suggest that this gene family is Tpl, name it the Osiris family, and suggest possible functions.