摘要Following translation,newly synthesized proteins must navigate a turbulent free energy landscape that threatens to trap them in misfolded or non-functional conformation. To reach their native states,many proteins are assisted by molecular chaperones that transiently facilitate folding and assembly without being part of the final structure.One such molecular scaffold is the heat shock protein 70 (HSP70) chaperone family,which acts in concert with Bcl-2-associated athanogene(BAG) co-chaperones to regulate a wide array of clients (Figure 1). By directly binding both a BAG protein and a client substrate,HSP70 acts as a versatile platform able to identify,retain,and effectively neutralize misfolded or mislocalized proteins. BAG proteins act as the decision-makers in this system,and modular interchange of the BAG family members BAG1-BAG6 influences client retention,localization,and degrative fate depending on the BAG protein bound. In a previous review discussing the diverse roles of BAG family proteins in mediating central nervous system (CNS) homeostasis,we performed an interactome analysis using publicly available datasets for all BAG family proteins except for BAG4,due to its limited expression in CNS contexts(Lin et al.,2025). In addition to expected canonical associations with HSP70 family members and the E3 ligase C-terminus of Hsc70-interacting protein,we were surprised to observe methyltransferase-like 3 (METTL3) as a common interactor of all BAG proteins examined.