A series of tandem duplications of an ancestral cathepsin L gene has given rise to a family of eight placenta-specific cathepsins in mice. These genes are differentially regulated both spatially and temporally and thus each can perform unique placental functions. Analysis of the function and expression of these genes is yielding new insights into gene regulation and proteolytic processes in placenta, and may dissect critical placental roles of the single human functional ortholog, cathepsin L.