GAGE6 (G antigen 6) is a cancer testis antigen encoding a tumor-associated protein presented by HLA class I molecules and recognized by CD8+ cytolytic T lymphocytes 1. Primary function: GAGE6 promotes cell proliferation and tumor formation when transcriptionally activated. Mechanism: GAGE6 transcription is regulated by the RNA/DNA-binding protein PSF (polypyrimidine tract-binding protein-associated splicing factor). Multiple regulatory RNAs—including vault RNAs (vtRNAs) and LINE-1 RNAs—bind PSF's RNA-binding domain, releasing it from the GAGE6 promoter and allowing transcriptional activation 23. PSF phosphorylation by NPM/ALK also suppresses PSF-mediated GAGE6 repression 4. Disease relevance: GAGE6 is expressed in 16% of pediatric rhabdomyosarcomas 1 and is overexpressed in paclitaxel- and doxorubicin-resistant cancer cell lines, correlating with chemotherapy resistance 5. GAGE6 overexpression directly promotes cell proliferation and colony formation 23. Clinical significance: Because GAGE6 expression is largely restricted to spermatogonia and placental cells in normal tissues while being prevalent in diverse cancers, it represents a promising immunotherapy target for chemotherapy-resistant tumors.