The folding energy landscape of the smallest protein, the 20-residue long Trp-cage, is more rugged than expected. Temperature-dependent NMR measurements revealed that at neutral pH the final step of the Trp-cage folding is a fast secondary structural rearrangement: the short α-helical G11–G15 segment of the intermediate (I) converts into a 310-helix and thus, the polypeptide adopts the most stable, folded (F) structure. At acidic pH the isomerization of the G11P12 peptide bond slows down the folding process: two off-pathway intermediate unfolded states (U′ and U′′) emerge. These two states have no native-like structure and show elevated internal mobility. For more information see the Full Paper by A. Perczel et al. on page 2628 ff.