EYA1 is a dual-function protein that acts as both a tyrosine phosphatase and transcriptional coactivator critical for organogenesis. As a phosphatase, EYA1 dephosphorylates histone H2AX at tyrosine 142, promoting efficient DNA repair and distinguishing repair responses from apoptotic pathways 1. As a transcriptional coactivator, EYA1 partners with SIX1 and related SIX family members in a regulatory network essential for craniofacial, skeletal, renal, and ear development 2. EYA1 is particularly important for inner ear development and sensory function, with specific enhancer elements (CNE16.39 and CNE16.45) driving tissue-specific expression in the inner ear sensory regions 3. Pathogenic EYA1 variants cause Branchio-oto-renal (BOR) syndrome, an autosomal dominant disorder accounting for approximately 40% of BOR cases 3. BOR syndrome presents with branchial arch anomalies, hearing impairment, ear malformations, and renal defects 45. EYA1 variants also associate with anterior segment anomalies and otofaciocervical syndrome. Prenatal presentation may include amniotic fluid abnormalities and cardiac defects, with variants in the conserved Eya Homologous Region affecting protein stability and phenotypic severity 6. In pediatric CAKUT cohorts, EYA1 variants represent significant genetic risk factors for progression to kidney failure 7.