BACKGROUND: A recent study identified NFXL1 as a candidate gene for specific language impairment. The protein encoded by this gene is predicted to be a transcription factor based on domain similarities with NFX1, a repressor of HLA class II genes, which have themselves been implicated in specific language impairment. However, there is very little literature on the function of NFXL1. METHODS: This report describes a study of NFXL1 expression in several human tissues and an investigation of differential expression in several specific brain regions through quantitative PCR as well as a study of the protein's sub-cellular localization in HEK cells and SH-SY5Y cells through immunofluorescence. RESULTS: The NFXL1 transcript was found in all investigated tissues. In the brain, a high level of NFXL1 expression was found in the cerebellum. An analysis of the sub-cellular localization of the protein showed a cytoplasmic pattern in the investigated cells. CONCLUSIONS: The NFXL1 transcript was present in samples from different tissues; in the brain, a high expression level was found in a region implicated in some language-related pathologies. NFXL1 did not show nuclear localization, suggesting that, if it regulates transcription, certain conditions may be required for it to translocate to the nucleus.