Mouse CLP-1, a potential cardiac transcriptional regulatory factor, is encoded by a single copy gene lacking introns that is expressed into two mRNAs via alternative polyadenylation. Both mRNAs encode the same 41 kDa protein, a novel protein that is 85.3% homologous with a human homologue called HIS1. Mouse CLP-1 is widely expressed in a number of tissues as well as in early development and is localized to the nucleus. The CLP-1 gene promoter is active in different cell types and sequence analysis shows a number of potential binding sites for cardiogenic transcription factors such as Nkx2.5 and GATA-4, indicating a potential role in development. CLP-1 appears to ‘squelch’ the cardiac MLC-2v promoter in a concentration-dependent manner in cardiac but not other cell types, suggesting that CLP-1 may be interacting with a cardiac-specific factor to regulate cardiac MLC-2v expression. The overall expression pattern of CLP-1 is similar to that of LCR-F1 and Oct-1, two widely expressed transcription factors that also play specific roles in the transcription of cell-specific genes. CLP-1 may be a transcriptional mediator capable of interacting with and potentiating cell-specific transcription factors.