A number of studies have reported an expanding list of heterogeneous SQSTM1/p62 mutations, localized to several different regions essential for protein function, in patients with both familial and sporadic ALS/FTLD; moreover, missense and truncating mutations in the same protein are thought to be causative of the chronic progressive skeletal disorder Paget’s disease of the bone (PDB). Here, SQSTM1 is linked to amyotrophic lateral sclerosis.