Cathepsin D (CatD) is an aspartic protease of the pepsin superfamily. It is constitutively expressed in nearly all cells, where it is trafficked to endosomes and lysosomes, and serves a role as a major acid hydrolase in intracellular protein turnover (reviewed in ref. 5). CatD localization and activation are regulated by multiple posttranslational processing steps . In breast cancer cells, CatD is often transcriptionally upregulated in a hormonally dependent fashion,6 and increased CatD expression has been found to correlate with tumor aggressiveness, metastasis and poor survival.7,8 CatD has been functionally linked to a number of mechanisms involved in cancer progression, including proliferation, invasion, metastasis and angiogenesis.7,8 In various breast cancer cell lines, the trafficking of pro-CatD through alternative pathways has been observed, resulting in differing degrees of extracellular secretion vs. lysosomal accumulation