Members of the leucine zipper tumor suppressor (LZTS) protein family are thought to play roles in cell growth modulation. The two currently known members were identified by analyzing genomic and chromosomal alterations reported to be either involved or deleted in various types of cancer, suggesting a causative relationship. By means of computational biology, we have now identified a novel member of the LZTS protein family named LZTS3. The corresponding gene was localized to chromosome 20p13 and consisted of three exons. The novel LZTS3 protein demonstrated a high similarity to LAPSER1/LZTS2 and FEZ1/LZTS1, two members of the LZTS family. The conserved FEZ1 domain contains a leucine zipper motif similar to the cAMP-responsive activating transcription factor 5. As FEZ1 inhibits cancer cell growth through the regulation of mitosis and its alteration resulted in abnormal cell growth, the LZTS3 protein was expected to have similar functions during cancer differentiation. Furthermore, the protein was conserved in vertebrates, as orthologs could be identified in mouse, rat, and zebrafish. The intracellular localization of the LZTS3 protein was predicted to be nuclear by means of Reinhardt's neural network and the k-nearest neighbor algorithm. An RT-PCR-based expression profile available from the human unidentified gene-encoded (HUGE) database demonstrated the highest expression in the brain and kidney, accompanied by lower expression in multiple other tissues.