Heparanase, an endo-β-D-glucuronidase that cleaves heparan sulphate and participates in extracellular matrix regulation, is upregulated in many primary human tumours and tumour-derived cell lines. It is produced as an inactive 65 kDa precursor that is cleaved into 50 kDa and 8 kDa subunits, which heterodimerize to form the active enzyme. To investigate heparanase processing, Israel Vlodavsky, Neta Ilan and co-workers have raised a polyclonal antibody to a 14-residue peptide in the N-terminus of the 50 kDa subunit (see p. 2249). They use this to show that, when the 65 kDa precursor is added to cells, both the 50 kDa subunit and the 65 kDa precursor localize to lysosomes. Because heparanase processing is sensitive to lysosomal protease inhibitors, the authors conclude that heparanase is activated in lysosomes rather than at the plasma membrane as previously suggested. Furthermore, because the polyclonal antibody inhibits heparanase activity, they suggest that monoclonal antibodies against the same epitope could help to tease out the normal and pathological roles of heparanase.