A 15.6 kb genomic clone encompassing the mouse procathepsin E gene was isolated and mapped. Sequencing revealed that the gene consists of nine exons followed by a polyadenylation signal at the 3'-end. The 5'-flanking region appears to be a TATA-less promoter but contains a nucleotide sequence that matches perfectly with the consensus motif of an initiator element [S.T. Smale, Biochim. Biophys. Acta 1351 (1997) 73-88.] to direct accurate initiation of transcription by RNA polymerase. This overlaps the site that was determined for the start of transcription. The absence of features considered typical of TATA-box regulated or housekeeping types of genes is consistent with the low levels of procathepsin E gene expression that are normally observed and might imply a unique sensitivity to or requirement for tissue-specific transcription factors that would account for the sporadic distribution of this aspartic proteinase in cells and tissues. The single copy of the procathepsin E gene was located on chromosome 1, near to that of mouse prorenin, a closely related aspartic proteinase involved in blood pressure regulation.