ZIC5 is a zinc finger transcription factor essential for neural crest development 1, containing five Cys2His zinc finger domains that enable sequence-specific DNA binding and transcriptional regulation 1. Beyond developmental roles, ZIC5 functions as a potent oncogenic transcription factor across multiple cancer types. In lung adenocarcinoma, ZIC5 promotes glycolysis and cell proliferation while suppressing disulfidptosis through metabolic reprogramming 2. ZIC5 was identified as a hub metastasis driver gene in lung adenocarcinoma 3. In hepatocellular carcinoma, ZIC5 activates the Wnt/β-catenin pathway to promote proliferation, migration, and invasion 4, and upregulates COL1A1 to enhance these malignant behaviors 5. In nasopharyngeal carcinoma, ZIC5 is regulated by the miR-101-3p/SOX2 axis and mediates cisplatin resistance 6. In pancreatic cancer, ZIC5 directly promotes RIOK3 expression to enhance cell survival 7. Clinically, elevated ZIC5 expression consistently correlates with poor patient prognosis across cancer types 254. ZIC5 represents a viable therapeutic target; compounds like patulin and LL-Z1640-2 that decrease ZIC5 protein levels selectively induce apoptosis in ZIC5-expressing cancer cells while sparing normal tissues with minimal ZIC5 expression 8.