Considering the suppression of B56δ expression in all liver cell types in HE and HO mice in this model and the ongoing controversy regarding the cell of origin of cHCC-CCA tumors [18,51,52], our data propose that Ppp2r5d may function either as a suppressor of biliary cell proliferation or as a (co-) determining factor in lineage commitment and cell fate of HPCs, in a chemically-induced carcinogenic context (see discussion). The gene discussed is PPP2R5D; the disease is cholangiocarcinoma.