GTF2H5 (general transcription factor IIH subunit 5) is a small 71-amino-acid protein component essential for the stability and function of the TFIIH transcription-repair complex 1. As a core TFIIH subunit, GTF2H5 is critical for nucleotide excision repair (NER), where TFIIH opens DNA around lesions to enable damaged oligonucleotide removal and replacement 2. The protein also supports RNA polymerase II transcription initiation through promoter opening and escape, with the complex's kinase module regulating RNA pol II phosphorylation 3. GTF2H5 maintains normal cellular TFIIH levels; mutations cause trichothiodystrophy type 3 (TTD3), an autosomal recessive neuroectodermal disorder characterized by brittle hair, photosensitivity, growth retardation, ichthyosis, and intellectual disability 45. Severe GTF2H5 mutations can present with life-threatening congenital ichthyosis, infections, and cardiac malformations in neonates 6. Notably, in ovarian cancer, low GTF2H5 expression correlates with improved survival and enhanced cisplatin chemosensitivity, suggesting the protein's role in DNA damage response modulates treatment outcomes 7. GTF2H5 also colocalizes with nuclear speckles and paraspeckles, indicating regulatory roles in gene expression 8.