GTF3C2 (general transcription factor IIIC subunit 2) is a critical component of the TFIIIC complex required for RNA polymerase III (Pol III)-mediated transcription. It functions as an essential factor for initiating transcription complex assembly on tRNA genes and enabling transcription of 5S rRNA and other stable nuclear and cytoplasmic RNAs 1. GTF3C2 expression is transcriptionally regulated by multiple factors: Sp1 controls GTF3C2 gene expression to modulate Pol III-directed transcription and cell proliferation 1, while TFAP2A positively regulates GTF3C2 expression as part of a broader mechanism controlling Pol III transcription machinery assembly 2. GTF3C2 has emerged as a disease-relevant gene across multiple cancer types. It functions as a novel fusion partner in Spitz melanocytic neoplasms, with documented GTF3C2-ALK fusion events identified in atypical Spitz tumors and spitzoid melanomas 3, and more recently in Spitz melanoma cases 4. In prostate cancer, GTF3C2 was identified as a novel African-specific fusion partner with TMPRSS2 in high-risk tumors from African patients, contributing to ethnic disparities in advanced disease 5. Additionally, GTF3C2 has been identified as a prognostic exosome-related immunosuppression gene in hepatocellular carcinoma, where its expression correlates with tumor microenvironment composition and patient outcome 6. Bioinformatics analyses suggest GTF3C2 may play roles in acute myocardial infarction pathology 7 and type 1 diabetes mellitus 8, though these associations require further validation.