TTR and amyloidosis: While genetic depletion of key secreted chaperones (e.g., HSF1-regulated TTR in the brain) offers a way to define these types of contributions, more information regarding the molecular mechanisms responsible for stress-responsive regulation of extracellular proteostasis is required to truly define the benefits of specific therapeutic approaches in mitigating pathologic imbalances of extracellular proteostasis in the context of amyloid diseases or other diseases associated with the misfolding and/or aggregation of secreted proteins.