The basic helix-loop-helix (bHLH) proteins control differentiation and development of a variety of organs. We have isolated the complementary DNA (cDNA) of a novel class of bHLH transcription factors. The previously uncharacterized bHLH messenger RNA (mRNA) was identified by RNA fingerprinting by comparing embryonic and adult mRNA. The reading frame sequence predicts a new class of bHLH family. Northern blotting of embryonic stages demonstrated a 3.2-kb transcript present in several embryonic tissues, including kidney, brain, heart, and lung, in a fashion confirmatory with the RNA-fingerprinting data. In situ hybridization of cryosections detected strong signals in the dorsal root ganglia of 14-day-old mouse embryos (E14). Transient transfection of human embryonic kidney cells with Nulp1-EGFP demonstrated nuclear localization. The complex expression pattern and unique protein sequence, including an acidic amino terminal and putative transcription activation domain, suggests that Nulp1 may have a distinct role in embryonic development of many organs, including the adult brain.