A novel mesenchymal protein, epimorphin, has been reported to play a key role in morphogenesis of fetal organs. The morphological and functional features of epimorphin in adult liver were entirely unknown. This study was performed to determine the distribution and function of this protein in the adult mouse liver. Epimorphin was detected on sinusoidal Ito cells. It played an essential role in the formation of hepatocyte spheroids which maintained differentiated function in primary culture. Therefore, Ito cells might control the differentiation of parenchymal hepatocytes in the adult liver in the pathologic condition as well as in fetal organs.