Gtf2h2, also known as general transcription factor II subunit H2, functions in nucleotide excision repair (NER) and basal transcription [7]. It is involved in the estrogen-dependent estrogen receptor alpha (ERα) signaling pathway, and plays a role in maintaining NER-related genomic stability and affecting PAM/NF-κB signaling pathway [7].

In hepatocellular carcinoma (HCC), overexpressing Gtf2h2 had no direct effect on endothelial cell viability, migration, or permeability, but GTF2H2-enriched exosomes from Huh7 cells could inhibit human umbilical vein endothelial cells (HUVECs) phenotypes such as proliferation and migration, suggesting potential use as a novel drug for treating HCC [1]. In lung cancer, TEP linc-GTF2H2-1 was significantly downregulated in patients, and its combination with other lncRNAs could improve the diagnostic efficiency of lung cancer [2]. In spinal muscular atrophy (SMA), GTF2H2 gene deletions were analyzed in patients, and a significant difference was found between healthy and SMA subjects. Pediatric patients with GTF2H2 deletions demonstrated higher motor functions [3,5,8,9,10]. In addition, GTF2H2 was identified as one of the genes significantly differentially expressed in the tissue of patients with neuropathic pain, suggesting it may be a potential therapeutic target [6]. The N-terminal region of the transcription factor E2F1 can recruit GTF2H2, and overexpression of GTF2H2 enhanced E2F1 activation of tumor suppressor genes and induction of cell death [4].

In conclusion, Gtf2h2 has diverse functions in different biological processes and diseases. In HCC, its exosome-derived form may have anti-angiogenesis potential; in lung cancer, it could be a biomarker; in SMA, it may be related to disease severity and motor function; in neuropathic pain, it may serve as a therapeutic target. Its interaction with E2F1 also impacts tumor suppressor gene activation. These findings from various studies help to understand the biological significance of Gtf2h2 in different disease contexts.