Paget's disease of bone (PDB) is the second most common metabolic bone disorder, 
after osteoporosis. It is characterised by focal areas of increased and 
disorganised bone turnover, coupled with increased bone formation. This disease 
usually appears in the late stages of life, being slightly more frequent in men 
than in women. It has been reported worldwide, but primarily affects individuals 
of British descent. Majority of PDB patients are asymptomatic, but clinical 
manifestations include pain, bone deformity and complications, like pathological 
fractures and deafness. The causes of the disease are poorly understood and it 
is considered as a complex trait, combining genetic predisposition with 
environmental factors. Linkage analysis identified SQSTM1, at chromosome 5q35, 
as directly related to the disease. A number of mutations in this gene have been 
reported, pP392L being the most common variant among different populations. Most 
of these variants affect the ubiquitin-associated (UBA) domain of the protein, 
which is involved in autophagy processes. Genome-wide association studies 
enlarged the number of loci associated with PDB, and further fine-mapping 
studies, combined with functional analysis, identified OPTN and RIN3 as causal 
genes for Paget's disease. A combination of risk alleles identified by 
genome-wide association studies led to the development of a score to predict 
disease severity, which could improve the management of the disease. Further 
studies need to be conducted to elucidate other important aspects of the trait, 
such as its focal nature and the epidemiological changes found in some 
populations. In this review, we summarize the clinical characteristics of the 
disease and the latest genetic advances to identify susceptibility genes. We 
also list current available treatments and prospective options.