Nuclear envelope rupture and resealing: mechanisms, consequences, and disease implications

The nuclear envelope (NE) establishes an essential physical separation between the nucleoplasm and cytoplasm in eukaryotic cells. Its structural integrity ensures selective molecular exchange through nuclear pores, a fundamental feature of eukaryotic cells. For this reason, it has long been assumed that the NE remains intact. However, recent studies revealed localized rupture of the NE in diverse physiological and pathological contexts. These ruptures can be resealed by endogenous mechanisms, suggesting that rupture-resealing dynamics contribute to homeostasis and are altered in disease. In the present review, we summarize physiological and pathological contexts in which NE rupture has been observed. We evaluate major hypotheses regarding its causes and consequences and discuss current understanding of the mechanisms and regulation of NE resealing. We conclude by highlighting key knowledge gaps in the pathophysiological roles of NE rupture and resealing.