Amyloid ion channels are a common structural link for protein-misfolding diseases. This study shows that amyloid proteins, including amyloid-β(1-40), α-synuclein, ABri, ADan, serum amyloid A, and amylin, undergo supramolecular conformational changes and form ion-channel-like structures in reconstituted membranes. These ion channels destabilize cellular ionic homeostasis, leading to cell pathophysiology and degeneration in amyloid diseases. Using atomic force microscopy, circular dichroism, gel electrophoresis, and electrophysiological recordings, the researchers demonstrated that these amyloid molecules form channel-like structures and elicit single ion-channel currents. The 3D structures of these globular amyloid peptides were analyzed, revealing that they form supramolecular structures with varying numbers of subunits. The study also showed that these amyloid ion channels can induce ion transport and disrupt ionic homeostasis, contributing to the pathophysiology of protein-misfolding diseases. The findings suggest that amyloid ion channels provide a direct pathway for inducing pathophysiological and degenerative effects in cells. The study highlights the importance of understanding the structural and functional properties of amyloid peptides in the context of protein-misfolding diseases.Amyloid ion channels are a common structural link for protein-misfolding diseases. This study shows that amyloid proteins, including amyloid-β(1-40), α-synuclein, ABri, ADan, serum amyloid A, and amylin, undergo supramolecular conformational changes and form ion-channel-like structures in reconstituted membranes. These ion channels destabilize cellular ionic homeostasis, leading to cell pathophysiology and degeneration in amyloid diseases. Using atomic force microscopy, circular dichroism, gel electrophoresis, and electrophysiological recordings, the researchers demonstrated that these amyloid molecules form channel-like structures and elicit single ion-channel currents. The 3D structures of these globular amyloid peptides were analyzed, revealing that they form supramolecular structures with varying numbers of subunits. The study also showed that these amyloid ion channels can induce ion transport and disrupt ionic homeostasis, contributing to the pathophysiology of protein-misfolding diseases. The findings suggest that amyloid ion channels provide a direct pathway for inducing pathophysiological and degenerative effects in cells. The study highlights the importance of understanding the structural and functional properties of amyloid peptides in the context of protein-misfolding diseases.