Chaperones in kinase homeostasis and drug discovery

Molecular chaperones play a central role in kinase homeostasis by guiding the folding, maturation, and stability of kinase clients. Yet advances in kinase folding and post-translational modification have not been adequately integrated into a coherent chaperone-centered framework, limiting a unified understanding of kinase homeostasis, and constraining more systematic efforts to target the chaperone-kinase axis. Recent structural and mechanistic studies now support a model in which chaperone assemblies function as regulatory platforms that coordinate kinase maturation, modification, and fate control. This review integrates these advances into a chaperone-centered view of kinase homeostasis and discusses pharmacological strategies targeting the chaperone-kinase axis, including chaperone modulation, interface disruption, and bifunctional approaches.