The article explores the structural and functional properties of amyloid molecules, which are known to cause protein misfolding diseases such as Alzheimer's, Huntington's, and Parkinson's. The authors use atomic force microscopy (AFM), circular dichroism (CD) spectrometry, gel electrophoresis, and electrophysiological recordings to study the 3D conformations and ion-channel activities of various amyloid peptides, including amyloid-β(1–40), α-synuclein, ABri, ADan, serum amyloid A, and amylin. They find that these peptides undergo supramolecular conformational changes when reconstituted in lipid bilayers, forming ion-channel-like structures. These channels can stabilize or destabilize cellular ionic homeostasis, leading to cell pathophysiology and degeneration. The study provides evidence that the globular conformations of amyloid proteins, rather than their fibrillar forms, are responsible for the cellular effects observed in conformational diseases. The findings highlight the importance of understanding the 3D structures of amyloid peptides in the context of their pathogenic mechanisms.The article explores the structural and functional properties of amyloid molecules, which are known to cause protein misfolding diseases such as Alzheimer's, Huntington's, and Parkinson's. The authors use atomic force microscopy (AFM), circular dichroism (CD) spectrometry, gel electrophoresis, and electrophysiological recordings to study the 3D conformations and ion-channel activities of various amyloid peptides, including amyloid-β(1–40), α-synuclein, ABri, ADan, serum amyloid A, and amylin. They find that these peptides undergo supramolecular conformational changes when reconstituted in lipid bilayers, forming ion-channel-like structures. These channels can stabilize or destabilize cellular ionic homeostasis, leading to cell pathophysiology and degeneration. The study provides evidence that the globular conformations of amyloid proteins, rather than their fibrillar forms, are responsible for the cellular effects observed in conformational diseases. The findings highlight the importance of understanding the 3D structures of amyloid peptides in the context of their pathogenic mechanisms.