TOR1AIP1-Associated Nuclear Envelopathies

Int J Mol Sci. 2023 Apr 7;24(8):6911. doi: 10.3390/ijms24086911.


Human TOR1AIP1 encodes LAP1, a nuclear envelope protein expressed in most human tissues, which has been linked to various biological processes and human diseases. The clinical spectrum of diseases related to mutations in TOR1AIP1 is broad, including muscular dystrophy, congenital myasthenic syndrome, cardiomyopathy, and multisystemic disease with or without progeroid features. Although rare, these recessively inherited disorders often lead to early death or considerable functional impairment. Developing a better understanding of the roles of LAP1 and mutant TOR1AIP1-associated phenotypes is paramount to allow therapeutic development. To facilitate further studies, this review provides an overview of the known interactions of LAP1 and summarizes the evidence for the function of this protein in human health. We then review the mutations in the TOR1AIP1 gene and the clinical and pathological characteristics of subjects with these mutations. Lastly, we discuss challenges to be addressed in the future.

Keywords: LAP1; LAP1B; LAP1C; TOR1AIP1; clinical spectrum; inner nuclear membrane; lamina-associated polypeptide 1B; lamina-associated polypeptide 1C; lamina-associated protein 1; mutations.

Publication types

  • Review

MeSH terms

  • Cytoskeletal Proteins* / metabolism
  • Humans
  • Membrane Proteins* / metabolism
  • Muscular Dystrophies* / metabolism
  • Mutation
  • Nuclear Envelope / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism


  • Membrane Proteins
  • Nuclear Proteins
  • TOR1AIP1 protein, human
  • Cytoskeletal Proteins

Grants and funding

This research received no external funding.