THRAP3 is a multifunctional transcriptional coregulator and RNA-binding protein with roles in splicing, transcriptional regulation, and cellular stress responses. Primary Function: THRAP3 functions in pre-mRNA splicing and remains associated with spliced mRNA through exon junction complex interactions 1. It regulates alternative splicing of specific genes including PTPRC/CD45 and controls mRNA stability of CCND1 1. THRAP3 acts as a coactivator of circadian clock regulation through the CLOCK-BMAL1 heterodimer and modulates PPARγ-dependent transcription in adipocytes 12. Mechanism: THRAP3 interacts with phosphorylated PPARγ at Ser273 to control diabetic gene programming 2. It suppresses AMPK-mediated autophagy in hepatocytes by direct binding and nuclear-cytoplasmic translocation regulation 3. THRAP3 promotes R-loop resolution via DDX5 interaction and methylation-dependent recruitment of XRN2 4. In AML, THRAP3 recruits SLU7 to facilitate GIT2 alternative splicing, promoting ferroptosis resistance 5. Disease Relevance: THRAP3 mutations occur in parathyroid carcinoma 6. THRAP3 is significantly overexpressed in blood cancers (DLBCL, BL, AML) and associated with poor prognosis and chemotherapy resistance 78. High THRAP3 expression correlates with poor AML prognosis and ferroptosis resistance 5. In BRAF-mutated colorectal cancer, nuclear PD-L1 inhibits THRAP3 to promote cell cycle progression 9. Clinical Significance: THRAP3 represents a potential therapeutic target in multiple cancers, type 2 diabetes, and NAFLD, with metformin-mediated THRAP3 suppression shown to inhibit MM cell proliferation 8.