SUN2 is a nuclear envelope protein that functions as a core component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex, mediating mechanical force transmission across the nuclear envelope and coupling the nuclear lamina to the cytoskeleton 1. Beyond its classical LINC function, SUN2 has emerged as a multifunctional protein with calcium-regulated roles in nuclear actin polymerization and active RNA polymerase II clustering, operating independently of its LINC-complex role 2. SUN2 coordinates with the formin INF2 at the nuclear envelope to assemble intranuclear actin filaments in response to calcium elevations, promoting signal-dependent spatial reorganization of transcriptionally active chr22 2. SUN2 dysfunction is implicated in multiple disease contexts. Mutations in SUN2 cause Emery-Dreifuss muscular dystrophy (EDMD), a rare condition characterized by muscle weakness, contractures, and life-threatening cardiac complications 1. In HGPS, SUN2 expression increases in response to progerin-induced nuclear stiffness, coupling with RhoA activation to promote cellular senescence and innate immune responses 3. Additionally, SUN2 interacts with NUP210 at the nuclear periphery to modulate mechanotransduction and suppress metastatic progression in breast cancer 4. Conversely, SUN2 is upregulated in medulloblastoma, particularly the SHH molecular subgroup, correlating with poor survival 5. Recent evidence also indicates SUN2-lamin A interactions are disrupted by CNS-enriched metabolites, impairing immunological synapse formation in tumor-immune evasion 6.