Huntington disease is a monogenic, autosomal dominant, progressive 
neurodegenerative disorder caused by a trinucleotide CAG repeat expansion in 
exon 1 of the huntingtin (HTT) gene; age of onset of clinical symptoms inversely 
correlates with expanded CAG repeat length. HD leads to extensive degeneration 
of the basal ganglia, hypothalamic nuclei, and selected cortical areas, and a 
wide range of molecular mechanisms have been implicated in disease pathology in 
animal or cellular models expressing mutated HTT (mHTT) proteins, either 
full-length or amino-terminal fragments. However, HD cellular models that 
recapitulate the slow progression of the disease have not been available due to 
the toxicity of overexpressed exogenous mHTT or to limitations with using 
primary cells for long-term studies. Most investigations of the effects of mHTT 
relied on cytotoxicity or aggregation end points in heterologous systems or in 
primary embryonic neuroglial cultures derived from HD mouse models. More 
innovative approaches are currently under active investigation, including 
screening using electrophysiological endpoints, as well as the recent use of 
primary blood mononuclear cells and of human embryonic stem cells derived from a 
variety of HD research participants. Here we describe how these cellular systems 
are being used to investigate HD biology as well as to identify mechanisms with 
therapeutic potential.