The MST1/2-SAV1-WWC1-3 (HPO1) and MAP4K1-7-NF2 (HPO2) Hippo signaling modules together regulate LATS1/2 kinases and YAP/TAZ; inactivation of either module in liver results in bile duct hyperplasia and intrahepatic cholangiocarcinoma. Here, MST1 is linked to intrahepatic cholangiocarcinoma.