This mechanistic insight opens two therapeutic avenues: By targeting the catalytic domain of NSUN2 responsible for site-specific m5C deposition on TP53 mRNA, we can develop selective inhibitors to block this oncogenic modification and hinder tumor progression; alternatively, designing small-molecule or peptide-based NSUN2 degraders offers a complementary strategy to suppress NSUN2-driven malignancy, collectively expanding the therapeutic landscape for NPC. Here, TP53 is linked to nasopharyngeal carcinoma.