To identify target genes at the gene-dense 15q15.1 endometrial cancer GWAS risk locus, we focussed on enhancers, crucial mediators of the effects of GWAS variation. Employing chromatin looping and inhibitory CRISPR analyses, we identified and validated enhancer/target gene pairs at this region. We further determined that risk variants within a validated enhancer increased the promoter activity of target genes, including CHST14, a key player in extracellular matrix formation. Transcriptional targeting of CHST14 inhibited cancer-related phenotypes (colony formation and anchorage-independent growth) in endometrial cancer cells, with subsequent transcriptomic and molecular analyses implicating processes related to DNA damage. This study lays the foundation for further investigation into the potential role of CHST14 in endometrial cancer development and its potential for therapeutic targeting.