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The tissue kallikreins are serine proteases encoded by highly conserved multigene families. The rodent kallikrein ( KLK ) families are particularly large, consisting of 13  26 genes clustered in one chromosomal locus. It has been recently recognised that the human  KLK  gene family is of a similar size (15 genes) with the identification of another 12 related genes ( KLK4 - KLK15 ) within and adjacent to the original human  KLK  locus ( KLK1 -3) on chromosome 19q13.4. The structural organisation and size of these new genes is similar to that of other  KLK  genes except for additional exons encoding 5 or 3 untranslated regions. Moreover, many of these genes have multiple mRNA transcripts, a trait not observed with rodent genes. Unlike all other kallikreins, the  KLK4-KLK15  encoded proteases are less related (25–44%) and do not contain a conventional kallikrein loop. Clusters of genes exhibit high prostatic ( KLK2-4 ,  KLK15 ) or pancreatic (KLK6-13) expression, suggesting evolutionary conservation of elements conferring tissue specificity. These genes are also expressed, to varying degrees, in a wider range of tissues suggesting a functional involvement of these newer human kallikrein proteases in a diverse range of physiological processes.

The Expanded Human Kallikrein ( KLK ) Gene Family: Genomic Organisation, Tissue-Specific Expression and Potential Functions