Embracing diversity: Post-translational modifications, the chaperone code, and the emergence of new chaperone entities

Dr Len Neckers played a pioneering role in establishing that HSP90 is regulated by post-translational modifications (PTMs), fundamentally reshaping how molecular chaperones are understood. This insight laid the foundation for what has become known as the "chaperone code," the concept that coordinated PTM patterns act as regulatory signals governing chaperone function, interactions, and stress responsiveness. In this short perspective, I reflect on how Len's early work seeded this conceptual shift and how subsequent advances have revealed that PTMs not only fine-tune canonical chaperone activities but can also enable chaperones to adopt non-canonical functional states under specific stress conditions. These developments have expanded the landscape of chaperone biology, illustrating how chemical encoding can diversify chaperone behavior and reconfigure protein networks. Together, they highlight the enduring impact of Len's contributions and the importance of embracing complexity in understanding chaperone function.