Paget's disease of bone is a chronic and metabolic bone disorder that is characterized by an increased bone turnover within discrete lesions throughout the skeleton. Mutations in the p62 gene, in particular in its UBA domain, can cause this illness [160] . A proposed model explaining how p62 mutations lead to the Paget's disease of bone is the following: mutations of the UBA domain cause an impairment in the interaction between p62 and ubiquitinated TRAF6 and/or CYLD, an enzyme deubiquitinating TRAF6, which in turn enhances the activation of the NF-κB signaling pathway and the resulting increased osteoclastogenesis (Figure 3(b) ) [160] . If proven, this molecular scenario could open the possibility of using autophagy enhancers as a therapy to cure Paget's disease of bone.