HTT and Huntington disease: Opposing arguments to loss of function mediated by a dominant negative mechanism are that human patients with minimal or no HTT protein production due to either HTT aberrant splicing and/or post-translational mis-regulation of HTT RNA (e.g., LOMARS patients) present an extreme juvenile phenotype that differs from the progressive neurodegeneration observed in adult HD patients (Lopes F. et al., 2016; Jung et al., 2021).