Significance Deficiencies or defects in nuclear lamins result in cell toxicity and cause multiple human diseases. Nuclear membrane (NM) ruptures have been implicated in both cell toxicity and disease pathogenesis, but the factors that modulate susceptibility to NM ruptures are unknown. We observed low levels of LAP2β, a chromatin-tethering inner NM protein, in nuclear lamin–deficient neurons and fibroblasts with frequent NM ruptures. Further reducing LAP2β expression markedly increased NM ruptures (without affecting rupture duration), whereas increasing LAP2β virtually abolished NM ruptures—even in cells subjected to mechanical stress. The discovery that increased expression of LAP2β in nuclear lamin–deficient cells prevents NM ruptures represents an unexpected and welcome insight into factors that modulate the structural integrity of the nuclear membranes.