Cathepsin L (ctsl), a lysosomal cyteine protease over expressed and secreted by cancer cells, has been implicated in a number of physiological and pathological processes including tumor cell proliferation and metastasis. In the present study we demonstrate that an unknown mRNA of human origin (Gene Bank accession number AF 217997) is a splice variant of human cathepsin L mRNA (hCATL A IV) and encodes a truncated form of cathepsin L (Δctsl) containing only 151 C-terminal amino acids. This isoform is cytotoxic to the mammalian cells. Transient transfection studies revealed that unlike ctsl, upon over expression in eukaryotic cells Δctsl is not secreted in to the media. Immunogold electron microscopy revealed its localization to nuclear, perinuclear and cytosolic regions. In view of its cytotoxic property, targeted expression of Δctsl in tumor cells may prove useful in the management of cancer.