The front cover picture shows structure models for human tau-tubulin kinase 1 (TTBK1). The electrostatic surface model of TTBK1 reveals two basic patches on the substrate binding face providing an explanation for the requirement for phosphorylation-primed substrates. The insert highlights the distinct backbone conformations upon binding of inhibitors. 3-[(6,7-Dimethoxyquinazolin-4-yl)amino]phenol (1) (magenta) binds with fast kinetics, with no structural change to the peptide bond L199–D200 compared with either the ATP–complex or apo structure. In contrast, binding of methyl 2-bromo-5-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)benzoate (2) (cyan) induces a flip of the peptide bond L199–D200, which coincides with slow kinetics. The analyses of TTBK1 binding to ligands with distinct characteristics could enable a fast track for structure-based ligand design of selective TTBK1 inhibitors. For more details, see the Full Paper by Yafeng Xue, Niek Dekker et al. on p. 1846 ff.