BAG4 (Bcl-2-associated athanogene 4) is a molecular chaperone regulator that functions as a negative regulator of mitochondrial homeostasis and apoptotic signaling. BAG4 contains a conserved BAG domain that binds to HSP70/HSC70 family proteins and modulates their chaperone activity by promoting substrate release 1. A critical function of BAG4 is preventing PRKN (Parkin) recruitment to damaged mitochondria, thereby inhibiting mitophagy 2. BAG4 also prevents constitutive TNF receptor signaling by functioning as a silencer of death domains (SODD) 3. Clinically, BAG4 is frequently overexpressed across multiple malignancies. In colorectal cancer with microsatellite instability, the USP14/BAG4/PRKN axis promotes chemoresistance and tumorigenesis by suppressing mitophagy 2. In gastric cancer, BAG4 overexpression correlates with poor prognosis and activates the PI3K/AKT/NF-κB/ZEB1 axis to promote invasion and metastasis 4. In acute myeloid leukemia, elevated BAG4 expression associates with poor overall survival (AUC=0.944), immune evasion, and apoptotic resistance 5. BAG4 is located within the frequently amplified 8p11.23 chr8 region in squamous cell carcinomas, breast cancers, and other malignancies 6, functioning as a cooperative oncogenic driver with other amplicon genes 7.