ERCC2 encodes an ATP-dependent 5'-3' DNA helicase that serves as a core component of the TFIIH transcription factor complex, playing dual roles in DNA repair and transcription initiation 1. The protein is essential for transcription-coupled nucleotide excision repair (NER), where it recognizes damaged DNA bases and facilitates DNA opening around lesions to enable excision and replacement of damaged oligonucleotides 2. In transcription, ERCC2 is required for promoter opening and escape during RNA polymerase II-mediated transcription initiation, acting as a bridge between the CDK-activating kinase (CAK) and core-TFIIH complex 1. The protein undergoes conformational changes that are stabilized by XPA to allow contact with single-strand DNA 3. ERCC2 polymorphisms, particularly Asp312Asn and Lys751Gln variants, have been extensively studied for cancer susceptibility. Meta-analyses demonstrate associations between these polymorphisms and increased risks for multiple cancers, including bladder cancer 4, pancreatic cancer 5, and esophageal squamous cell carcinoma 6. Additionally, increased ERCC2 expression correlates with aggressive tumor phenotypes in head and neck cancers, showing significant associations with tumor stage, grade, and Ki-67 proliferation markers 7. These findings highlight ERCC2's critical importance in maintaining genomic stability and its potential as a cancer biomarker.