DEPDC1B (DEP domain containing 1B) is a cell cycle regulator that functions as a context-dependent oncogene controlling cell proliferation and migration. In myoblasts, DEPDC1B drives proliferation and prevents premature myogenic differentiation by regulating cell cycle regulators independently of canonical Wnt signaling 1. In multiple cancer types, DEPDC1B promotes malignant progression through distinct mechanisms: in breast cancer, DEPDC1B mediates USP5-dependent deubiquitination of β-catenin to activate Wnt/β-catenin signaling and enhance invasion/migration 2; in colorectal and lung cancers, DEPDC1B promotes proliferation and migration while suppressing apoptosis via NUP37-dependent PI3K/AKT pathway activation and CCNB1 upregulation 34; in multiple myeloma, DEPDC1B inhibits p53 signaling while upregulating CCNB1 5. Notably, in colon adenocarcinoma specifically, high DEPDC1B expression correlates with favorable prognosis, lower EMT status, and enhanced immune infiltration with responsiveness to anti-PD-L1 immunotherapy 6. DEPDC1B is regulated by B-Myb transcriptional control 4 and serves as an independent prognostic biomarker in hepatocellular carcinoma 7. These findings establish DEPDC1B as a promising therapeutic target across multiple cancer types, though tissue-specific contexts significantly influence its functional outcomes.