Protein phosphatases are enzymes that remove phosphate groups from proteins and play key roles in essential cellular processes. Their dysregulation contributes to diseases such as cancer, immune diseases, and heart failure. Accordingly, there is a great interest to study their mechanisms, substrates and druggability, as well as to validate them as disease targets.1 Our work focuses on specific phosphatases that drive the study of biological processes and the development of chemical tools. As research tools to enable studying and targeting these challenging enzymes we develop peptides, peptidomimetics, peptide libraries, bifunctional molecules, and also small molecules.2-4 Using these tools, we study phosphatases on the molecular and cellular level, and we also devise phosphoproteomic strategies to provide insights into their substrates and affected pathways.4,5 In addition, as a resource to the field we run an open access database www.DEPOD.org.6 I will discuss our work exemplified through the ubiquitous phosphatase PP1. [1] M. Köhn, ACS Cent. Sci. 2020, 6, 467-477.[2] J. Chatterjee, M. Beullens, R. Sukackaite, J. Qian, B. Lesage, D. Hart, M. Bollen, M. Köhn, Angew. Chem. Int. Ed. 2012, 51, 10054–10059.[3] A. Hoffmann, J. Weyershaeuser, Y. Chand, R. Geißen, N. Höfflin, B. Hoeger, M. Köhn, Bioorg. Med. Chem. 2025, 131, 118412.[4] B. Hoermann, T. Kokot, D. Helm, S. Heinzlmeir, J.E. Chojnacki, T. Schubert, C. Ludwig, A. Berteotti, N. Kurzawa, B. Kuster, M.M. Savitski, M. Köhn, Nat. Commun. 2020, 11, 3583.[5] B. Hoermann, E.-M. Dürr, C. Ludwig, M. Ercan, M. Köhn, Chem. Sci. 2024, 15, 2792-2804.[6] N. Damle, M. Köhn, Database (Oxford). 2019, 2019, baz133.