GTF2H4 (general transcription factor IIH subunit 4) is a component of the TFIIH complex that stimulates the ATPase activity of the XPB/ERCC3 subunit 1. The protein functions in two critical cellular processes: transcription initiation by RNA polymerase II and nucleotide-excision repair (NER) of DNA damage. GTF2H4 participates in the core TFIIH complex and associates with transcription factor TFIID, operating in the nucleoplasm and nuclear speckles. Beyond its canonical roles, GTF2H4 has emerged as a key regulator of cellular stress responses, with evidence that it is significantly enriched in transcriptional responses to myocardial ischemia-reperfusion injury 2. Clinically, GTF2H4 expression correlates with cancer progression. High GTF2H4 expression in prostate cancer associates with poor prognosis, predicting biochemical recurrence with superior accuracy compared to other TFIIH subunits (HR=2.47, P<0.001) 3. Genetic variants in GTF2H4 are associated with increased lung cancer susceptibility, with the rs114596632 variant showing functional relevance through decreased DNA repair capacity and mRNA expression 4. Additionally, GTF2H4 methylation patterns are altered in age-related macular degeneration 5 and associated with aggressive behavior development 6. Mutations in GTF2H4 can cause xeroderma pigmentosum complementation group XP-J, a DNA repair disorder 7, while Ronin transcriptional regulation of GTF2H4 modulates DNA damage responses in pluripotent stem cells 8.