Transcription factor 19 (TCF19) is a multifunctional biomolecule located within the major histocompatibility complex (MHC) class I region on chromosome 6p21.3. Structurally, TCF19 contains a plant homeodomain (PHD) finger that recognizes histone H3 lysine 4 trimethylation (H3K4me3) and a forkhead-associated (FHA) domain with yet-uncharacterized functions. Emerging evidence positions TCF19 as a multifunctional regulator associated with cell cycle progression, transcriptional regulation, cancer progression, and immune modulation through epigenetic and signaling mechanisms. This review provides the first systematic synthesis of TCF19’s structural domains, regulatory networks, and context-dependent functions across cancer and non-cancer diseases. We highlight critical knowledge gaps, including the unresolved function of its FHA domain and the lack of direct small-molecule inhibitors. In cancer, TCF19 drives proliferation, metastasis, immune evasion, and therapy resistance. Beyond cancer, TCF19 is involved in metabolic diseases, chronic infections, inflammatory disorders, and sensory deficits. TCF19 serves as a promising molecular biomarker for cancer diagnosis, prognosis, and treatment response monitoring, though direct targeting strategies remain unavailable.
Li et al. (Fri,) studied this question.