While further studies will be required to assess the specific molecular mechanisms mediated by ERK1/2 and p38 to impair the localization status of canalicular transporters in estrogen-induced cholestasis, our results strengthen the idea that there is a clear interplay between signalling cascades and intracellular trafficking in this cholestasis, and that both MAPKs are key players in its ethiology. This evidence concerns the gene MAPK3 and cholestasis.