Interestingly, recessive mutations of the HECT domain and ankyrin repeat-containing ubiquitin ligase E3 (HACE1) gene, coding for a ubiquitin ligase that ubiquitinates optineurin and ensures its interaction with p62/SQSTM1, are associated with mitochondrial dysfunction and severe damage to nervous system development [97], and experimental HACE1 knockout causes dysfunction of astrocyte mitochondria and provokes the development of astrogliosis in a model of Huntington’s disease [98]. Here, SQSTM1 is linked to juvenile Huntington disease.