Homeodomain transcription factors play important roles in directing cellular proliferation and differentiation. A TALE-superclass homeodomain protein, multifunctional repressor of TGF beta-induced transcription. Here we report identification of TGIF2, a novel TALE-superclass homeodomain protein that shows distinct homology with TGIF, especially in its DNA-binding domain. TGIF2 is expressed ubiquitously in human tissues, with the highest levels being found in heart, kidney, and testis. The TGIF2 product contains a putative nuclear localization signal; translocation of the protein to the nucleus was confirmed by transfection of epitope-tagged cDNA, TGIF2 lies on chromosome 20q11.2-12. Since amplification of 20q is often observed among ovarian cancers, we determined the status of DNA copy-number and expression of TGIF2 in 14 ovarian-cancer cell lines, This gene was overexpressed in all lines that showed amplification by FISH analysis. The results suggested that TGIF2 may play an important role in the development and/or progression of some ovarian tumors through a mechanism of gene amplification.