PTOV1 (Prostate Tumor Overexpressed 1) is an oncogenic adaptor protein that functions as a transcriptional regulator promoting cell proliferation across multiple cancer types. At the molecular level, PTOV1 acts through diverse mechanisms: it directly binds transcription factors like ZNF449 to enhance MYC transcription in colorectal cancer 1, antagonizes Notch signaling by suppressing HES1 and HEY1 expression to promote prostate cancer progression 2, and promotes translation via RACK1 interaction 3. PTOV1 localization is tightly regulated—phosphorylation at S36 by SGK2 enables 14-3-3 binding, which stabilizes PTOV1 in the cytosol and prevents HUWE1-mediated proteasomal degradation 4. Notably, PTOV1 drives p53 destabilization through SQSTM1-directed autophagic degradation, a key mechanism in colorectal cancer progression 5. Clinically, PTOV1 is significantly overexpressed in multiple malignancies including colorectal, prostate, esophageal, and urothelial cancers, correlating with advanced tumor stage, reduced survival, and poor prognosis 67. Additionally, PTOV1 acts as a testosterone-responsive gene promoting vascular smooth muscle cell proliferation in atherosclerosis 8. These findings establish PTOV1-targeting therapeutic strategies as promising approaches for multiple cancers.