GTF2E2 (general transcription factor IIE subunit 2) is a critical component of the RNA polymerase II transcription initiation machinery. Its primary function is to recruit TFIIH to the preinitiation complex and stimulate TFIIH's kinase and ATPase activities, with both factors required for promoter clearance 1. GTF2E2 operates within the nucleoplasm and nucleus, interacting with transcription factor complexes to facilitate transcription initiation 1. Beyond canonical transcription, GTF2E2 demonstrates broader oncogenic roles. Pan-cancer analysis reveals elevated GTF2E2 expression in most malignancies, with diagnostic potential across 20 cancer types 1. In endometrial carcinoma, GTF2E2 knockdown inhibits cell proliferation, migration, and invasion while inducing ferroptosis through GPX4 downregulation and ACSL4 upregulation 1. In glioblastoma, GTF2E2 upregulates CDC20 expression and promotes malignant progression, with expression regulated by miR-340-5p 23. GTF2E2 also functions as a rate-limiting subunit in transcription factor complex assembly 4. Clinically, biallelic GTF2E2 mutations cause non-photosensitive trichothiodystrophy (NPS-TTD), characterized by cysteine-deficient brittle hair and neuroectodermal abnormalities 56. GTF2E2 emerges as both a potential cancer biomarker and therapeutic target.