PAX1 is a paired-box transcription factor that functions as a sequence-specific DNA-binding transcriptional activator with critical roles in embryonic development and disease 1. During skeletal development, PAX1 is essential for vertebral column formation; PAX1-expressing vertebral skeletal stem cells (vSSCs) are physiologic mediators of vertebral bone formation, and genetic blockade of vSSC-derived osteoblasts results in defects in the vertebral neural arch and body 2. PAX1 also plays a key role in thymus development—biallelic loss-of-function PAX1 mutations cause syndromic severe combined immunodeficiency (SCID) associated with otofaciocervical syndrome type 2, with altered transcriptional profiles affecting genes involved in thymic and pharyngeal pouch-derived tissue development 3. PAX1 mutations represent inborn errors of immunity affecting lymphoid compartment development and IFN-γ antimycobacterial immunity 4. Beyond developmental roles, PAX1 is frequently silenced by methylation in cancers and functions as a tumor suppressor gene 56. PAX1 methylation serves as a promising biomarker for cervical cancer screening and triage of high-risk HPV-positive women, demonstrating superior diagnostic performance compared to cytology alone, with sensitivity and specificity of 77-85% and 91% for detecting cervical intraepithelial neoplasia 7. Hypermethylation of PAX1 has also been identified in epithelial ovarian cancer, esophageal squamous cell carcinoma, head and neck squamous cell carcinoma, and endometrial carcinoma 6.