Synaptic dysfunction significantly contributes to the pathogenesis of HD,565 with vesicular zinc playing a significant role in synaptic function.566,567 Specifically, increased levels of zinc have been measured in HD patients, suggesting that mutant Htt (mHtt) may disturb zinc metabolism.568 mHtt decreased ZnT3 expression by suppressing the conjugation of Sp1 with ZnT3 promoter.569 As a result, it downregulates vesicular zinc levels in the brains of N171-82Q HD transgenic mice. The gene discussed is SP1; the disease is Huntington disease.