Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization. As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning. May be involved in nucleus-centrosome attachment. During interkinetic nuclear migration (INM) at G2 phase and nuclear migration in neural progenitors its LINC complex association with SUN1/2 and probably association with cytoplasmic dynein-dynactin motor complexes functions to pull the nucleus toward the centrosome; SYNE1 and SYNE2 seem to act redundantly in cerebellum, midbrain, brain stem, and other brain regions except cerebral cortex and hippocampus. Required for centrosome migration to the apical cell surface during early ciliogenesis. May be involved in nuclear remodeling during sperm head formation in spermatogenesis; a probable SUN3:SYNE1/KASH1 LINC complex may tether spermatid nuclei to posterior cytoskeletal structures such as the manchette. Core component of LINC complexes which are composed of inner nuclear membrane SUN domain-containing proteins coupled to outer nuclear membrane KASH domain-containing nesprins. SUN and KASH domain-containing proteins seem to bind each other promiscuously; however, differentially expression of LINC complex constituents can give rise to specific assemblies. At least SUN1/2-containing core LINC complexes are proposed to be hexameric composed of three protomers of each KASH and SUN domain-containing protein. The SUN2:SYNE1/KASH1 LINC complex is a heterohexamer; the homotrimeric cloverleave-like conformation of the SUN domain is a prerequisite for LINC complex formation in which three separate SYNE1/KASH1 peptides bind at the interface of adjacent SUN domains. Self-associates. Interacts with SYNE3. Interacts with SUN3; proposed to form a spermatogenesis-specific LINC complex with SUN3 during sperm head formation. May interact with MUSK. Interacts with SPAG4/SUN4. Interacts with EMD and LMNA in vitro. Interacts with F-actin via its N-terminal domain. Interacts with DCTN1 and DYNC1I1/2; suggesting the association with the dynein-dynactin motor complex. Interacts (via KASH domain) with TMEM258 (By similarity). The largest part of the protein is cytoplasmic, while its C-terminal part is associated with the nuclear envelope, most probably the outer nuclear membrane. In skeletal and smooth muscles, a significant amount is found in the sarcomeres (By similarity). Expressed in C2F3 and CH310T1/2 cells, brain and skeletal muscle (at protein level). The KASH domain, which contains a transmembrane domain, mediates the nuclear envelope targeting and is involved in the binding to SUN1 and SUN2 through recognition of their SUN domains. The disulfid bond with SUN1 or SUN2 is required for stability of the respective LINC complex under tensile forces. Incomplete sequence. Belongs to the nesprin family.