David Rubinsztein’s is a Wellcome Trust Senior Clinical Fellow in Cambridge. His initial interests were in cholesterol metabolism, but he has made his major impact in neurodegenerative disorders caused by triplet repeat expansions, the paradigm for which is Huntington’s disease. During his clinical training period, David Rubinsztein contributed influential papers on the range of mutational sizes associated with disease, and on mutational bias, in relation to Huntington’s. Subsequently he has pursued the pathogenesis of neurodegeneration, by characterising cellular and biochemical abnormalities in diseases with CAG expansions. He set up novel model systems in cell culture, validated the behaviour of these models, and has produced a string of papers on the cellular effects of triplet expansions in Huntington’s and other diseases. His most recent work has taken the group forward from cell models, to screens for modifier loci in mice and to establishing mutants in zebra fish and rodents. The ingenious zebrafish models for screening potential therapeutic compounds he has developed in collaboration with Bill Harris and others constitute a major contribution to the field and hold the promise of clinical advance.