Toward a thermodynamic taxonomy of amyloid fibrils.

In this issue of Structure, Connor et al.1 combine topology and residue-level energetics of α-synuclein and tau fibrils to identify isoenergetic fold families. They reveal how conserved hotspot residues, mutations, and, potentially, environmental cues steer polymorph selection, providing a unified framework for comparing amyloid strains and classifying emergent structures.