Basic helix-loop-helix (bHLH) transcription factors play important roles in differentiation processes during embryonic development of vertebrates. ATOH8 (MATH6) is a tissue-restricted member of the atonal superfamily of bHLH transcription factors that exhibits 43-57% identity in the bHLH domain with other mammalian atonal paralogs including the NeuroD and Neurogenin factors. In the mouse, ATOH8 has been implicated in the specification and differentiation of neuronal cell lineages in the brain and may also participate in kidney development. Recent studies show that ATOH8 is a novel component of the pancreatic transcriptional network during embryonic development and suggest a potential role as a modulator of the differentiation program initiated by the pro-endocrine factor Neurog3. It is indispensable for early embryonic development, suggesting a more widespread function for this factor in tissue-specific differentiation processes that are dependent on class II bHLH genes.