PRRX2 is a paired-related homeobox transcription factor that functions as a sequence-specific DNA-binding transcription factor regulating RNA polymerase II-mediated transcription. Beyond its proposed developmental role in scarless wound healing during early gestation, PRRX2 has emerged as a critical regulator in multiple cancer types through distinct molecular mechanisms. In glioblastoma, PRRX2 functions as a ferroptosis suppressor by transcriptionally upregulating GCH1, which generates the antioxidant tetrahydrobiopterin (BH4) 1. In breast cancer, PRRX2 promotes progression through Wnt/β-catenin signaling activation and epithelial-mesenchymal transition (EMT) induction; silencing PRRX2 inhibits proliferation, invasion, and metastasis while reversing these processes 2 3. In hepatocellular carcinoma, PRRX2 directly binds and activates the ATOX1 promoter, promoting carcinogenesis and inhibiting cuproptosis 4. In pancreatic cancer, PRRX2 transcriptionally activates GLI2 to promote hedgehog signaling, thereby inhibiting senescence and enhancing malignancy 5. In prostate cancer, PRRX2 activation drives enzalutamide resistance through CDK4/6/Rb/E2F and BCL2 pathway alterations 6. Conversely, PRRX2 attenuation enhances transdifferentiation of adult skin fibroblasts to neurons when combined with ASCL1 and p53 knockdown 7.