In addition to coding for virion structural proteins and the reverse transcriptase, all mammalian hepadnaviruses also contain an open-reading frame called X, because its function could not be fathomed from the deduced amino acid sequence. While it is now known that the woodchuck virus (and presumably the other hepadnaviruses, as well) cannot replicate in the animal host if the X gene is mutated, the exact function of the X protein in the viral life cycle is still unknown. In transient transfection studies, X protein has been shown to trans-activate a wide variety of promoters. The mechanism of this activation is also unclear, although there is accumulating evidence in favor of both a cytoplasmic effect involving signal transduction pathways, and a nuclear effect directly on the transcriptional machinery. It appears that the X protein is at least as complex as many of the other, better studied viral trans-activators, and may well yield new insights into mammalian cell functions in the future. Copyright 1996 S. Karger AG, Basel