Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy with limited therapeutic options and poor prognosis.1,2 Despite recent advances in surgical techniques and systemic therapies, the molecular drivers of ICC progression remain incompletely understood. Coiled-coil domain-containing proteins (CCDCs) are increasingly recognized for their roles in tumor biology. Among them, CCDC178 has emerged as a candidate oncogene in certain cancers, but its role in ICC has not been previously elucidated.3 In this study, we identify CCDC178 as a key oncogenic regulator in ICC and reveal its mechanistic function through leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4)-dependent signaling and immune modulation.