Pagetic bone lesions also occur in a variety of complex genetic disorders, such as those involving profilin 1 and valosin-containing protein/p97 [15, 16], but these multisystem proteinopathies are early onset and have extra-skeletal symptoms along with multiple bone lesions, unlike the late onset, solitary presentation of common Paget’s disease [17]. This evidence concerns the gene VCP and Paget disease.