KLK3 and Familial prostate cancer: Based on prior studies done with recombinant Granzyme B [22], we hypothesized that the replacement of the N-terminal pro-peptides of GZMB and TRP with a peptide substrate that is selectively and efficiency cleaved by PSA [4] would yield zymogens that would be inactive in normal tissues but efficiently activated by high levels of enzymatically active PSA present in the ECF of prostate cancer sites (Figure 1).