While p97 deletion results in early embryonic lethality (Müller et al., 2007), a series of missense mutations lead to very specific malfunctions in protein homeostasis linked to degenerative disorders (Watts et al., 2004), among them Inclusion Body Myopathy associated with Paget disease of the bone and Frontotemporal Dementia (IBMPFD), a lethal autosomal dominant disorder with onset in midlife. Here, VCP is linked to inclusion body myopathy with Paget disease of bone and frontotemporal dementia.