NUP50 encodes nucleoporin 50, a nuclear pore complex component with dual roles in nuclear transport and gene regulation. As a nuclear transport protein, NUP50 facilitates protein import by displacing nuclear localization signals from importin-alpha and promoting importin recycling 1. It localizes to nuclear pores through interaction with Nup153, which provides scaffolding for its transport functions 1. Beyond transport, NUP50 has emerged as a key regulator of cellular metabolism and longevity. It is post-translationally regulated by AMPK in response to energy stress and directly interacts with transcriptional machinery through its intrinsically disordered region to activate lipid catabolism genes, promoting lifespan extension 2. In DNA repair, NUP50 works with Nup153 to promote 53BP1 recruitment to damage sites, counteracting BRCA1-mediated events and influencing the balance between homologous recombination and non-homologous end joining 3. Clinically, NUP50 mutations are associated with increased ALS risk, with loss of function causing neuronal death and motor defects 4. The protein also serves as an autoantigen target in type 1 diabetes and Sjögren's disease, particularly in seronegative patients 56.