DEPDC1 (DEP domain containing 1) functions as a transcriptional corepressor involved in negative regulation of DNA-templated transcription. The DEPDC1-ZNF224 complex may suppress apoptosis in bladder cancer cells by repressing A20 transcription and promoting NF-κB nuclear translocation. Across multiple cancer types, DEPDC1 drives malignant progression through distinct mechanistic pathways. In renal cell carcinoma, DEPDC1 promotes glycolysis and tyrosine kinase inhibitor resistance via the AKT/mTOR/HIF1α pathway 1. In hepatocellular carcinoma, DEPDC1 enhances proliferation and chemotherapy resistance through JNK signaling, with elevated expression associated with poor overall survival 2. DEPDC1 also facilitates progression in nephroblastoma via PI3K/Akt/mTOR signaling 3, in oral squamous cell carcinoma through interaction with FOXM1 and Wnt/β-catenin signaling 4, and in liposarcoma by modulating KIF20A 5. Pan-cancer analysis reveals DEPDC1 upregulation in 29 of 33 human cancers, with roles in cell cycle regulation, DNA repair, and T cell exhaustion 6. Clinically, elevated DEPDC1 expression consistently predicts poor prognosis and metastasis across tumor types. DEPDC1 represents a therapeutic target for combination strategies, particularly metabolic therapy combined with tyrosine kinase inhibitors in advanced renal cell carcinoma 1, and may serve as a cancer biomarker for diagnosis and prognosis assessment.