A new discovery published in Nature Structural & Molecular Biology (Naseri NN et al. Nat Struct & Mol Biol 27(2):192-201; 2020) clarifies the mechanism behind a neurodegenerative lysosomal storage disease: Mutations in cysteine string protein-α (CSPα) cause its aggregation and adult-onset neuronal ceroid lipofuscinosis (ANCL or Kufs disease). Abnormal binding of Fe-S clusters to CSPα mutants is shown to drive this disease-causing aggregation, which can be reversed in neurons by clinically approved iron chelators https://www.nature.com/articles/s41594-020-0375-y