LBH is a transcription factor as a candidate gene for CHD associated with partial trisomy 2p syndrome. To identify potential LBH-interacting partners, a yeast two-hybrid screen using LBH as a bait was performed with a human heart cDNA library. One of the clones identified encodes alphaB-crystallin. Co-immunoprecipitation and GST pull-down assays showed that LBH interacts with alphaB-crystallin, which is further confirmed by mammalian two-hybrid assays. Co-localization analysis showed that in COS-7 cells, alphaB-crystallin that is cytoplasmic alone, accumulates partialy in the nucleus when co-transfected with LBH. Transient transfection assays indicated that overexpression of LBH or alphaB-crystallin reduced the transcriptional activities of p53 and p21, respectively, Overexpression of both alphaB-crystallin and LBH together resulted in a stronger repression of the transcriptional activities of p21 and p53. These results showed that the interaction of LBH and alphaB-crystallin may inhibit synergistically the transcriptional regulation of p53 and p21.