BACKGROUND: The rise in endometrial cancer rates globally calls for advanced diagnostic methods and new biomarkers. CPA4, known for its role in cancer development, has not yet been studied in relation to endometrial cancer, making it a promising research avenue. METHODS: We analyzed CPA4's mRNA expression using data from TCGA and GEO databases and validated these findings with 116 clinical samples through immunohistochemical analysis. The Ishikawa and Hec-1-A cell lines were used to examine CPA4's functionality. In addition, we conducted correlation analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and survival analysis to understand CPA4's role in endometrial cancer prognosis. A nomogram model was developed for clinical prognostic predictions. RESULTS: CPA4 is significantly overexpressed in endometrial cancer, correlating with tumor progression and poor prognosis. Overexpression is linked to crucial functions, such as mitosis and cell cycle. Reducing CPA4 in cell lines inhibited tumor growth and spread. Kaplan-Meier plots and Cox regression analysis confirmed CPA4's significance in prognosis, with our predictive model showing high accuracy. CONCLUSIONS: CPA4 emerges as a vital biomarker for diagnosing and prognosing endometrial cancer, presenting a novel pathway for research and clinical application. The study highlights its potential as a clinical tool, paving the way for improved patient management and treatment strategies in endometrial cancer.