Multisystem proteinopathy (MSP) is a pleiotropic inherited disorder classically involving inclusion body myopathy, frontotemporal degeneration, Paget disease of bone, and sometimes motor neuron disease or parkinsonism.[1][2] The best-characterized form is caused by pathogenic variants in VCP, linking MSP to proteostasis failure, organelle quality control, and stress response biology.[1:1]
MSP is a proteostasis disorder. VCP/p97 participates in ubiquitin-dependent protein quality control, endoplasmic-reticulum associated degradation, autophagy, lysophagy, mitophagy, and DNA damage responses.[1:2] When those pathways fail, muscle, bone, and nervous-system phenotypes can emerge in different combinations across patients and families.[1:3][2:1]
Valosin-Containing Protein (VCP): A Review of Its Diverse Molecular Functions and Clinical Phenotypes. International Journal of Molecular Sciences (2024). ↩︎ ↩︎ ↩︎ ↩︎
Clinical Classification of Variants in the Valosin-Containing Protein Gene Associated With Multisystem Proteinopathy. Neurology Genetics (2023). ↩︎ ↩︎