The Fall of the Armor: Lamin Dysregulation and a Wide Network of Laminopathies

The nuclear membrane of cells harbors a lamina as a critical structural component beneath itself which serves as a dynamic scaffold that maintains nuclear integrity and cellular homeostasis. The primary component of the nuclear lamina is lamins, a set of type V intermediate filament proteins, which form a meshwork to provide mechanical stability while modulating essential biological processes like DNA replication, chromatin organization, and gene expression via mechanotransduction. The clinical significance of lamins is exemplified by laminopathies, a heterogeneous group of genetic disorders arising from mutations in the genes encoding the proteins (LMNA for A-type lamins [A and C], LMNB1 for lamin B1, and LMNB2 for lamin B2) that manifest in the form of a variety of pathologies comprising muscular dystrophies, premature aging syndromes, cardiovascular abnormalities, and metabolic aberrations. Laminopathies, though rare, form the basis of many life-threatening conditions that lack potent therapeutic interventions. Lamins have also been shown to be dysregulated in a multitude of cancers, and research has uncovered a diabolical role of lamins in oncogenesis. The understanding of laminopathies and dysregulation of lamins resulting in disorders is critical in developing novel therapeutic strategies through drug repurposing and epigenetic modulation to curb the burden of the diseases.