The Critical Assessment of Computational Hit Finding (CACHE) challenges are prospective benchmarking exercises modeled after CASP where computational chemists and data scientists use their methods to predict small-molecule ligands for a pre-defined protein target . But unlike CASP, CACHE challenges are prospective: predicted molecules are tested experimentally and all data shared publicly. The goal of CACHE is to delineate the state-of-the-art in computational hit discovery, an area poised for breakthroughs driven by advances in artificial intelligence (AI). The first CACHE challenge (CACHE #1), focused on the WDR domain of LRRK2, a Parkinson's disease target. An apo structure of the targeted domain was available in the protein data bank (PDB), but no ligand had been reported at the time. CACHE #1 reflected a highly dynamic and explorative field; a few weakly active molecules were discovered, indicating that significant progress remains to be seen .