Junctional adhesion molecule-like protein (JAML) is gaining attention in cancer biology; however, its role in EC remains unclear.<h4>Methods</h4>This study integrated multi-omics data (TCGA, pan-cancer analysis and single-cell transcriptomics), dual independent clinical cohorts (TCGA dataset and an institutional cohort), and <i>in vitro</i>/<i>in vivo</i> experimental models to systematically analyze JAML expression patterns, clinical relevance, and tumor-progression regulatory mechanisms in EC. This evidence concerns the gene JAML and cancer.