SYNE1 encodes nesprin-1, a critical component of the LINC (Linker of Nucleoskeleton and Cytoskeleton) complex that maintains subcellular spatial organization by forming linking networks between organelles and the actin cytoskeleton 1. The protein plays essential roles in nucleocytoplasmic interactions, facilitating transmission of mechanical forces across the nuclear envelope and controlling nuclear movement and positioning 2. SYNE1 is required for centrosome migration during early ciliogenesis and may be involved in nuclear remodeling during spermatogenesis through LINC complex formation with SUN proteins 2. Mutations in SYNE1 are associated with multiple neuromuscular disorders, including Emery-Dreifuss muscular dystrophy type 4, spinocerebellar ataxia type 8, and arthrogryposis multiplex congenita type 3 13. The gene is frequently mutated in cerebellar ataxia patients, ranking among the top five most commonly affected genes in targeted sequencing studies 34. SYNE1 mutations have also been identified in satellite cell dysfunction affecting muscle regeneration capacity 5 and show associations with female reproductive health conditions, potentially through hormonal regulation mechanisms 6. The protein's role in nuclear membrane integrity makes it clinically significant for cardiac complications common in associated muscular dystrophies.