Functional amyloids in secretory granules of the pituitary and other organs may serve as a normal biological function for storing peptide and protein hormones, contrary to their association with diseases like Alzheimer's and type II diabetes. The study shows that hormones are stored in an amyloid-like cross-β-sheet-rich conformation in secretory granules. This structure is stable and allows for controlled release of monomeric hormones upon secretion. The research demonstrates that many hormones form amyloid-like aggregates in the presence of heparin, a GAG, and that these aggregates can release functional monomers. Amyloid-like structures in secretory granules are confirmed by various biophysical methods, including electron microscopy, Thio T binding, circular dichroism, and x-ray fiber diffraction. The study also shows that some hormones, like ACTH and β-endorphin, coaggregate in amyloid-like structures, and that these aggregates are not toxic in the context of secretory granules. The findings suggest that amyloid-like structures in secretory granules are not only stable but also functional, supporting the hypothesis that hormones are stored in this form. The study also highlights the potential for amyloid-like structures to be involved in the storage and release of hormones in the pituitary, hypothalamus, and pancreas, contrasting with their traditional association with disease. The research challenges the "amyloid hypothesis" by showing that amyloid-like structures can be functional and not necessarily toxic. The study provides direct evidence that secretory granules of the mouse pituitary tumor neuroendocrine cell line AtT20 are composed of amyloids, and that these granules contain hormones in an amyloid-like conformation. The findings suggest that amyloid-like structures in secretory granules may play a crucial role in the storage and release of hormones, and that their function is regulated by various factors, including the presence of helper molecules and the processing of prohormones. The study also highlights the potential for amyloid-like structures to be involved in the pathogenesis of diseases, and the need for further research to understand the relationship between amyloid aggregation and function in the body.Functional amyloids in secretory granules of the pituitary and other organs may serve as a normal biological function for storing peptide and protein hormones, contrary to their association with diseases like Alzheimer's and type II diabetes. The study shows that hormones are stored in an amyloid-like cross-β-sheet-rich conformation in secretory granules. This structure is stable and allows for controlled release of monomeric hormones upon secretion. The research demonstrates that many hormones form amyloid-like aggregates in the presence of heparin, a GAG, and that these aggregates can release functional monomers. Amyloid-like structures in secretory granules are confirmed by various biophysical methods, including electron microscopy, Thio T binding, circular dichroism, and x-ray fiber diffraction. The study also shows that some hormones, like ACTH and β-endorphin, coaggregate in amyloid-like structures, and that these aggregates are not toxic in the context of secretory granules. The findings suggest that amyloid-like structures in secretory granules are not only stable but also functional, supporting the hypothesis that hormones are stored in this form. The study also highlights the potential for amyloid-like structures to be involved in the storage and release of hormones in the pituitary, hypothalamus, and pancreas, contrasting with their traditional association with disease. The research challenges the "amyloid hypothesis" by showing that amyloid-like structures can be functional and not necessarily toxic. The study provides direct evidence that secretory granules of the mouse pituitary tumor neuroendocrine cell line AtT20 are composed of amyloids, and that these granules contain hormones in an amyloid-like conformation. The findings suggest that amyloid-like structures in secretory granules may play a crucial role in the storage and release of hormones, and that their function is regulated by various factors, including the presence of helper molecules and the processing of prohormones. The study also highlights the potential for amyloid-like structures to be involved in the pathogenesis of diseases, and the need for further research to understand the relationship between amyloid aggregation and function in the body.