Paget's disease of bone is a focal disorder of aging bone. The classic 
late-onset Paget's disease is often caused by a P392L mutation in the gene 
SQSTM1, which disturbs signaling pathways in osteoclasts on cell activation. 
This prevalent mutation is neither necessary nor sufficient to cause Paget's 
disease. Its identification, along with the elucidation of other mutations 
underlying early-onset Paget's and Paget's disease seen in association with 
inclusion body myopathy and frontotemporal dementia, have redefined our 
understanding of genetic disorders of bone remodeling by emphasizing the 
importance of environmental determinants in their pathophysiology.