YWHAZ (14-3-3ζ) is an adapter protein that regulates diverse signaling pathways through binding to phosphoserine/phosphothreonine motifs on target proteins 1. The protein modulates partner activity upon binding and promotes cytosolic retention of transcription factors like TFEB 1. YWHAZ facilitates interferon-γ signaling by interacting with EFHD2 in myeloid cells and promoting IFNγR2 translocation to the plasma membrane, contributing to immune and inflammatory responses in non-alcoholic steatohepatitis 2. In multiple myeloma, YWHAZ stability is enhanced through ENO1-mediated acetylation while antagonizing ubiquitination, leading to mitophagy activation and drug resistance to bortezomib 3. Mutations in YWHAZ cause Cardiofaciocutaneous syndrome, a rare RASopathy affecting the RAS-MAPK signaling pathway with cardiac, facial, and neurological manifestations 4. The gene serves as a stable reference for qPCR normalization in colorectal cancer radiotherapy studies and extracellular vesicle research 56. YWHAZ is also implicated in telomere length regulation and shows potential as a prognostic marker in breast cancer 78.