ERCC3 encodes an ATP-dependent 3'-5' DNA helicase that serves as a critical component of the TFIIH transcription factor complex, functioning in both RNA polymerase II-mediated transcription and nucleotide excision repair (NER). The protein binds double-stranded DNA and exhibits translocase activity rather than classical helicase function 12. In transcription, ERCC3's ATPase activity is essential for promoter opening and escape during initiation, inducing DNA twisting to facilitate transcription complex assembly 34. For DNA repair, ERCC3 helps open DNA around lesions to enable damaged oligonucleotide excision and replacement 5. Disease associations include xeroderma pigmentosum and trichothiodystrophy, reflecting its DNA repair role. Recent studies suggest broader clinical relevance: ERCC3 mutations are associated with breast cancer susceptibility in multiple populations, including African American and Chinese cohorts 67. The gene shows potential as a prognostic biomarker, with expression negatively correlating with estrogen receptor status in breast cancer 7. Additionally, ERCC3 promoter methylation appears linked to benzene-induced hematotoxicity and environmental disease susceptibility 89, highlighting its importance beyond classical DNA repair disorders.