When considering lowering strategies, maintaining certain physiological levels of HTT is important—hypomorphic HTT mutations cause a neurodevelopmental disorder, LOMAR syndrome,43 and common HTT genetic variation linked to ageing and cognitive traits.19 The results of a new paradigm-changing study that performed paired single-cell gene expression and CAG-repeat length analysis in human Huntington’s disease brains also bring the field’s focus on HTT lowering under scrutiny.44 Firstly, striatal neuron loss did not correlate with HTT expression levels. Here, HTT is linked to juvenile Huntington disease.