HMBS and occipital horn syndrome: One characteristic manifestation of copper dyshomeostasis is neurodegenerative disease, seen in classical Mendelian copper disorders such as Menkes disease, occipital horn syndrome (OHS), and Wilson’s disease (WD).6–8 The ubiquitin proteasome system (UPS) participates in the degradation of cytosolic, nuclear, and transmembrane proteins and plays an important role in neurodevelopment.9,10 Multiple UPS proteins have been demonstrated to interact with the copper homeostasis machinery.