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MUTATIONS in two genes, PS1 and PS2, coding for the presenilins, have been linked to the early onset form of familial Alzheimer's disease (AD). Here we report the identification of a Drosophila melanogaster homologue of human PS genes, Dps, which maps to band 77B-C on chromosome 3 and is expressed at multiple developmental stages. The predicted amino acid sequence of the Dps product is 53% identical to human presenilins, with the greatest similarity in the putative transmembrane domains, the hydrophobic domains at the beginning and the end of the cytoplasmic TM6-TM7 loop and the C-terminus. Analysis of Dps in a genetically tractable model system such as Drosophila may provide insight into the mechanisms of Alzheimer's disease (AD) necessary for the development of rational therapeutic approaches.