LEMD2 is an inner nuclear membrane protein essential for nuclear envelope (NE) integrity and organization. As a transmembrane ESCRT adaptor, LEMD2 recruits CHMP7 and downstream ESCRT-III proteins to orchestrate NE reformation during mitosis 1. During nuclear reassembly, LEMD2 undergoes phase separation, condensing around microtubule spindles to form a macromolecular O-ring seal facilitating early nuclear sealing 1. The protein binds BAF through its LEM motif, initiating NE rupture repair mechanisms critical for maintaining genome stability 2. Beyond mitotic functions, LEMD2 interacts with SATB2 to regulate activity-dependent nuclear shape plasticity in neurons and control expression of cognition-related genes 3. LEMD2 mutations cause severe disease consequences. The p.L13R mutation disrupts BAF interaction, impairing NE rupture repair and leading to dilated cardiomyopathy with fibrosis and ventricular arrhythmias in humans and mouse models 24. Complete loss of LEMD2 causes neonatal lethality due to cardiac abnormalities and extensive DNA damage 4. LEMD2 deficiency promotes micronuclear collapse through aberrant CHMP7 oligomerization under oxidative stress, driving chr6 rearrangements 5. Additionally, LEMD2 mutations cause Marbach-Rustad progeroid syndrome, presenting with skeletal abnormalities and premature aging phenotypes 6. LEMD2 is thus fundamental for cardiac homeostasis, genome stability, and neuronal function.