A direct connection between calpain overactivation and autophagy deregulation has yet not been made for HD; however, the knockdown of a calpain homologue in an HD Drosophila model and CAST overexpression in HD mice reduced polyQ toxicity of an N-terminal huntingtin fragment and improved behavioral signs, by activating autophagy [164]. The gene discussed is CAST; the disease is Huntington disease.