Sequestosome 1 is an adapter protein which binds ubiquitin and may regulate the activation of NFKB1 by TNF-alpha, nerve growth factor and interleukin-1. It may regulate signaling cascades through ubiquitination and may also be involved in cell differentiation, apoptosis, immune response and regulation of K(+) channels. It is present as a homooligomer or heterooligomer and localises to the cytoplasm, late endosome and nucleus. In cardiac muscles it localises to the sarcomeric band. It accumulates in neurofibrillary tangles and in Lewy bodies of neurons from individuals with Alzheimer and Parkinson disease respectively. It is also enriched in Rosenthal fibers of pilocytic astrocytoma and in liver cells it accumulates in Mallory bodies associated with alcoholic hepatitis, Wilson disease, indian childhood cirrhosis and in hyaline bodies associated with hepatocellular carcinoma. Sequestosome 1 is ubiquitously expressed and to date, there are 2 named isoforms produced by alternative splicing. Defects in sequestosome 1 cause sporadic and familial Page disease of bone (PDB). This is a metabolic bone disease characterised by focal areas of increased and disorganised bone turn-over due to activated osteoclasts.