ZIC5 (Zinc Finger of the Cerebellum 5) is a C2H2-type zinc finger protein belonging to the ZIC family. This protein plays an important role in neural development, participating in neural crest cell differentiation, neural tube formation, and the establishment of the left-right axis. Recent studies have found that ZIC5 is significantly overexpressed in various malignant tumors, including colon cancer, prostate cancer, cervical cancer, lung cancer, hepatocellular carcinoma, and melanoma. It promotes tumor cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) by activating the Wnt/β-catenin signaling pathway. ZIC5 enhances cancer stem cell properties and is positively correlated with the expression of stemness markers. It serves as an independent prognostic marker for colon cancer, and its high expression is closely associated with poor patient survival.