Serine protease inhibitors, or serpins, are a family of protease inhibitors that use a complex mechanism of conformational change in order to inhibit target proteases. Although the structural mechanism of serpin function is well characterised, the biological roles and targets of many serpins remains elusive. The genome of Drosophila melanogaster contains 29 serpin-encoding genes, however very few have been functionally characterised. Among the few characterised Drosophila serpins, Serpin42Da (Spn42Da) is of particular interest as it encodes 10 different isoforms that are predicted to have distinct sub-cellular localisations and different target specificity. To investigate the roles of Spn42Da to help predict target proteases we over-expressed Spn42Da transgenes in various Drosophila tissues. We found that over-expressing the Spn42Da-A isoform in ovarian follicle cells using slbo-Gal4 causes embryos to be laid with a fragile eggshell due to defects in the cross-linking of the inner-most eggshell layer, the vitelline membrane. As Spn42Da-A has previously been shown to inhibit the serine proteases Furin1 (Fur1) and Furin2 (Fur2) in vitro, we examined these proteases as candidate targets for Spn42Da-A. Genetic interaction experiments between spn42Da-A and the Furin proteases revealed that spn42Da-A interacts with Fur2 in the follicle cells during eggshell biogenesis. We are currently performing additional genetic interaction experiments between spn42Da-A and Fur1, and investigating the effect of both Fur1 and Fur2 RNAi knockdown on eggshell biogenesis. Finally, we have also generated a spn42Da null mutant which we are currently testing for interactions with Fur1 and Fur2. Taken together, this study will provide fundamental insight into the molecular mechanisms surrounding Drosophila eggshell biogenesis, and lead to a greater understanding of the serpins and proteases involved in producing this complex structure.