SNUPN encodes snurportin-1, a nuclear import adapter that mediates trimethylguanosine (m3G)-cap-dependent nuclear import of U snRNPs, essential spliceosomal components 1. The protein binds specifically to m3G-capped U snRNAs and functions through oligomerization and interaction with importin-β to facilitate snRNP nuclear transport 23. Biallelic SNUPN variants cause limb-girdle muscular dystrophy (LGMDR29), a previously unrecognized disease entity 123. Pathogenic variants impair snurportin-1 function, leading to cytoplasmic accumulation of snRNP components, defective spliceosomal maturation, and widespread splicing dysregulation—particularly in genes governing muscle development and cytoskeletal organization 12. Clinical manifestations include proximal weakness starting in childhood, restrictive respiratory dysfunction, myofibrillar-like features with myotilin deposits, and Z-disc disorganization 13. Beyond muscular dystrophy, SNUPN shows pleiotropic associations across diseases. Proteome-wide Mendelian randomization studies identified SNUPN as causally associated with reduced bioavailable testosterone via elevated SHBG 4, decreased osteosarcopenia risk 5, and reduced Type 2 diabetes risk 6. Genetic variants in SNUPN are associated with breast cancer susceptibility 7.