BCL2-associated athanogene 3 (BAG3) (BAG3)

BCL2-associated athanogene 3 (BAG3) is a multifunctional co-chaperone protein predominantly expressed in cardiomyocytes and skeletal muscle, where it serves as a critical regulator of proteostasis and structural integrity [1, 2]. It localizes to the Z-disc of the sarcomere, acting as a scaffold that coordinates the activity of heat shock proteins, such as HSP70 and HSPB8, to facilitate chaperone-assisted selective autophagy (CASA) [2, 3]. This pathway is essential for the degradation of mechanically damaged proteins, ensuring the maintenance of the cardiac contractile apparatus [3, 4]. Mutations in the BAG3 gene or reduced protein expression are strongly associated with the development of dilated cardiomyopathy (DCM) and progression to heart failure [4, 5]. Therapeutic strategies currently under investigation include AAV-based gene therapies to restore BAG3 levels and small molecules designed to modulate its interaction with HSP70 [5, 6]. While primarily studied for its cardioprotective role, BAG3 is also implicated in the survival of various cancer cells, which presents a significant safety challenge for systemic therapeutic modulation [1, 6].

Other names

BAG family molecular chaperone regulator 3BCL2-binding athanogene 3BISCAIR-1MFM6

BAG3 acts as a co-chaperone that links the HSP70 system to the macroautophagy pathway, specifically through chaperone-assisted selective autophagy (CASA), to maintain sarcomere integrity and protein quality control in cardiomyocytes [2, 3].