Abstract PACE4 has been identified as a second human subtilisin-like protease by Keifer et al. [DNA and Cell Biology (1991) 10, 757-769]. In this study, we isolated two novel cDNAs coding for PACE4 isoforms (PACE4C and PACE4D) from a human placenta cDNA library. The deduced PACE4C protein sequence (652 amino acids) lacks the cysteine-rich region located at the carboxy terminus of PACE4. The DNA sequence of the 3′-untranslated region (1 kb) of PACE4C is not homologous to the PACE4 sequence. The protein (497 amino acids) encoded by PACE4D cDNA lacks a signal peptide, a propeptide and the cysteine-rich region. These isoform cDNAs were also isolated from rat pituitary cDNA library.