Single-cell analysis revealed that EDY-positive epithelial cells exhibited elevated oncogenic pathway activity and enhanced IL17-IL17RC signaling, possibly due to the loss of KDM5D in epithelial cells and altered epigenetic regulation.<h4>Conclusions</h4>LOY/EDY can be detected in OPMD and promotes malignant progression by altering oncogenic signaling and epithelial cell interactions. Here, IL17RC is linked to oculopharyngeal muscular dystrophy.