THRAP3 is an RNA-binding protein with pleiotropic roles in mRNA splicing, stability, and transcriptional regulation. Functionally, it associates with the exon junction complex and remains bound to spliced mRNA, where it can trigger mRNA decay independent of nonsense-mediated decay pathways. THRAP3 regulates signal-induced alternative splicing and modulates mRNA stability through the SNARP complex; it also participates in DNA damage responses and circadian clock regulation as a coactivator of CLOCK-BMAL1. In disease contexts, THRAP3 dysregulation is implicated in multiple malignancies. High THRAP3 expression correlates with poor prognosis in acute myeloid leukemia (AML), where it promotes ferroptosis resistance through SLU7-mediated alternative splicing of GIT2 1. In diffuse large B-cell lymphoma, Burkitt's lymphoma, and AML, THRAP3 is overexpressed relative to normal blood cells and associated with shorter overall survival 2. THRAP3 mutations have been identified in parathyroid carcinoma 3, and nuclear PD-L1 promotes BRAF-mutated colorectal cancer proliferation via THRAP3 inhibition 4. Loss of THRAP3 increases sensitivity to DNA-damaging agents and impairs repair of DNA damage 5. Clinically, metformin suppresses multiple myeloma cell proliferation and apoptosis by reducing METTL3-mediated m6A methylation of THRAP3, offering a potential therapeutic mechanism 6. THRAP3 also modulates metabolic disease: antisense oligonucleotide-mediated knockdown of hepatic THRAP3 improves hyperglycemia and insulin resistance in high-fat-fed mice 7, and liver-specific THRAP3 knockout ameliorates nonalcoholic fatty liver disease by enhancing AMPK-mediated autophagy 8.