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Lamin-associated polypeptide 1B (LAP1B)
- Target
- LAP1B
- Molecular classification
- Integral membrane protein, Inner nuclear membrane protein, Nuclear envelope protein, Lamina-associated protein, Other
01
Overview
Lamin-associated polypeptide 1B (LAP1B), encoded by the TOR1AIP1 gene, is an integral membrane protein of the inner nuclear membrane where it binds A- and B-type lamins and interacts directly with TorsinA, modulating its ATPase activity and facilitating localization to the nuclear envelope. LAP1B is essential for nuclear membrane integrity, proper assembly of the nuclear lamina, regulation of chromatin, and migration of fibroblasts. Mutations in TOR1AIP1 cause a spectrum of rare recessively inherited diseases including limb-girdle muscular dystrophy, congenital myasthenic syndromes with impaired neuromuscular transmission, multisystem disorders, and cardiomyopathy, often leading to significant functional impairment and early death. LAP1B participates in key cellular and tissue-specific processes but is not currently an established therapeutic target for small molecule or biologic drugs.
- Other names
- Torsin-1A-interacting protein 1TOR1AIP1LAP1LAP1BLAP1CFLJ13142Lamin-associated polypeptide 1BLamina-associated polypeptide 1BLamina-associated protein 1LGMD2Y
02
Mechanism of action
Null; no known drugs directly target LAP1B/TOR1AIP1.
03
Biological functions
Maintenance of nuclear membrane integrityChromatin bindingModulation of ATPase activity (activation of TorsinA and TorsinB ATPase activity)Regulation of nuclear lamina assembly and membrane attachmentCell migrationRegulation of cellular growth, proliferation, and survivalSignal transductionProtein–protein interaction (e.g., lamins, TorsinA/B, phosphatase PP1, TRF2)
04
Disease associations
Limb-girdle muscular dystrophy (LGMD2Y)Muscular dystrophy, autosomal recessiveCongenital myasthenic syndromeCardiomyopathyMultisystemic disorders (may include progeroid features)Nonalcoholic fatty liver disease and nonalcoholic steatohepatitisDystonia (in rare cases)Other nuclear envelopathies
05
Safety considerations
Lack of targeted therapies; therapeutic challenges relate to managing multisystem disease and early mortality in affected patientsNo safety concerns for direct pharmacological targeting because no current therapies exist
06
Interacting drugs
No drugs with direct known interaction are reported in current scientific or clinical databases. The gene and protein are primarily related to monogenic diseases and not established as a direct pharmacological target.
07
Biomarkers
Absence or reduced levels of LAP1B and LAP1C (as determined by muscle biopsy/immunohistochemistry) in patients with relevant genetic syndromesMutations in TOR1AIP1 gene for patient selection (genetic diagnosis of LGMD2Y and congenital myasthenic syndrome)
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