WHR1 (winged helix repair factor 1) is a DNA-binding protein essential for transcription-coupled nucleotide excision repair (TC-NER), a pathway that removes DNA lesions blocking RNA polymerase II (RNAPII) transcription 1. WHR1 functions as a core component of the TC-NER complex, directly interacting with stalled RNAPII and downstream DNA 2. The protein facilitates recruitment of the TFIIH helicase complex by interacting with XPD, guiding it to DNA damage sites for removal 3. WHR1 promotes RNAPII ubiquitination and regulates UVSSA repositioning within the TC-NER complex, enabling timely lesion access by downstream repair factors 4. Beyond DNA repair, WHR1 possesses RNA-binding capacity and regulates mRNA expression levels 1. The protein exhibits protein serine/threonine kinase activity and mediates single-strand break repair processes [GO annotations]. Defects in TC-NER mechanisms are implicated in xeroderma pigmentosum and other cancer-prone conditions; however, specific disease associations for WHR1 mutations are not detailed in available abstracts. WHR1's dual functionality in both DNA damage recognition and transcriptional regulation suggests broader cellular roles beyond lesion removal, warranting further investigation into disease relevance and clinical applications.