Similarly, although RNF216 (TRIAD3), another RBR-type E3, has been linked to the neurodegenerative disorder Gordon–Holmes syndrome (49) and its activity is enhanced by phosphorylation and K63-linked di-Ub (50), neither the subcellular localization of the activated protein nor its substrates are known. The gene discussed is RNF216; the disease is Cerebellar ataxia - hypogonadism.