WW domain-containing proteins are found in all eukaryotes and play an important role in the regulation of a wide variety of cellular functions such as protein degradation, transcription, and RNA splicing. The cloning and characterization of a novel human WW domain-containing gene, hWW45, which encodes a protein of approximately 45 kDa consisting of 2 WW domains and a coiled-coil region is reported here. The murine homologue cDNA, mWW45, displays a different 3′-untranslated region and predicts a protein identity of 93% to hWW45. Northern blot and RT-PCR analysis demonstrated that both mWW45 and hWW45 transcripts are ubiquitously expressed in adult tissues. The mouse embryonic expression is first seen at 7 days post coitum in Northern blot analysis of whole embryos. Chromosomal localization by radiation hybrid mapping revealed that hWW45 is localized at chromosome 14, 10.31cR from the marker D14S269.