Furthermore, (a) the unequivocal detection of Penk in our BDL mice liver, (b) the presence of Met-enkephalin immunoreactivity in cholestatic rat46 and human liver48, and (c) the accumulation of PENK-derived endogenous opioids in livers of rats with cholestasis indicate the importance of PENK in human cholestasis44. The gene discussed is PENK; the disease is cholestasis.