BAG3 is a co-chaperone and adapter protein that functionally connects heat shock proteins (HSP70s and small heat shock proteins) to regulate protein homeostasis 12. As a nucleotide-exchange factor, BAG3 promotes ADP release from HSP70s by binding to their nucleotide-binding domain, triggering client protein release 13. BAG3 exhibits anti-apoptotic activity and regulates HSF1 nucleocytoplasmic transport 45. Clinically, BAG3 mutations cause multiple neuromuscular and cardiac diseases. BAG3 mutations are established causes of myofibrillar myopathy, characterized by Z-disk disintegration and myofibrillar degradation 67, and dilated cardiomyopathy with potential rapid progression 8. In cardiomyocytes, BAG3 loss increases transforming growth factor-β receptor 2 (TGFBR2) levels through reduced ubiquitination and degradation, promoting cardiac fibrosis 8. BAG3 also plays protective roles in neurodegeneration. Neuronal BAG3 attenuates tau hyperphosphorylation and cognitive deficits following traumatic brain injury by regulating autophagy-lysosome pathways 9. In Alzheimer's disease, astrocyte BAG3 induction enhances clearance of α-synuclein and tau through macroautophagy 10, while elevated BAG3 stabilizes BACE1, the rate-limiting amyloid-β generating enzyme 11.