TIFAB (TIFA inhibitor) is an FHA domain-containing protein that negatively regulates innate immune signaling by inhibiting TIFA-mediated TRAF6 activation, potentially through conformational changes in TIFA 1. As a critical modifier of TRAF protein function, TIFAB suppresses canonical NF-κB signal transduction 1. Beyond its immune regulatory role, TIFAB plays important functions in hematopoiesis and developmental processes including cochlear, genitalia, and palate morphogenesis, as well as neuromuscular and gastrointestinal processes. In hematologic malignancies, TIFAB enhances KMT2A::MLLT3-induced acute myeloid leukemia (AML) by modulating metabolic pathways through the HNF4A transcription factor via inhibition of NF-κB component RelB 2. TIFAB deletion in AML impairs leukemia stem/progenitor cell engraftment, glucose uptake, and mitochondrial function, reducing expression of MYC, HOXA9/MEIS1, and mTORC1 signaling genes 2. Clinically, TIFAB dysregulation is implicated in hematologic disorders and myelodysplastic neoplasms 1, suggesting therapeutic potential in targeting TIFAB-dependent signaling in leukemia treatment.