POTEE (POTE ankyrin domain family member E) is a cancer-testis antigen that functions primarily as an oncogenic protein in multiple malignancies. At the molecular level, POTEE localizes to the cytoplasm 1 and regulates cancer cell behavior through multiple signaling pathways. In colorectal cancer, POTEE promotes tumorigenesis via the SPHK1/p65 signaling axis, enhancing cell growth, cycle progression, and inhibiting apoptosis 2. Additionally, POTEE activates the Rac1/Cdc42 pathway to promote migration, invasion, and epithelial-mesenchymal transition 1. In breast cancer, POTEE enhances mitochondrial oxidative phosphorylation (OXPHOS), promoting malignant progression; this function is negatively regulated by lncRNA LINC00667 through TRIM33-mediated ubiquitination 3. Disease relevance: POTEE is significantly upregulated in colorectal cancer, ovarian cancer (97.2% of patients), breast cancer, and lung cancer, consistently predicting poor prognosis 245. Clinical significance: POTEE mutations in lung adenocarcinoma correlate with superior responses to immune checkpoint inhibitors, with 100% objective response rate compared to 27.7% in wild-type patients 6. Serum POTEE levels independently predict progression-free survival in non-small-cell lung cancer 5. POTEE peptides are recognized as immunogenic tumor antigens, generating antigen-specific CD8 T cell responses 4, positioning POTEE as a promising target for antigen-targeted immunotherapy.