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MAPK plays an important role in transmitting the extracellular signaling to its intracellular targets. P14/Mp1 scaffold protein complex orchestrates signaling through Raf/MEK/ERK cascade at late endosomes by means of linking the MEK1 and ERK1/2 together at endosomal compartment. Previous studies indicated the significance of p14 in cell cycle regulation and cellular proliferation in mouse embryonic fibroblasts. Herewith, possible gene and protein targets of p14 were identified by exploiting conditional p14 liver KO mice and primary hepatocyte cultures. Using a regeneration model based on carbon tetrachloride induced liver injury, a reduction of the proliferation rate in regenerating livers of p14 KO mice was discovered. All together these data suggest an important role of p14 mediated late endosomal MAPK signaling in cell cycle progression and proliferation in vivo.