The propeptide is nonessential for the expression of human cathepsin D.

When the 44-amino acid propeptide of human procathepsin D was deleted by mutagenesis in vitro, the mature protein was stably expressed and secreted from transfected mammalian cells. The secreted protein was correctly folded as judged by its binding to pepstatinylagarose. We were unable to detect lysosomal targeting of the propeptide-deleted protein, and targeting was not restored by the substitution of the propeptides from pepsin or renin. We conclude that its propeptide is not essential for the folding of nascent cathepsin D. Efficient lysosomal targeting in mammalian cells appears to require the precursor form of the molecule.