Nup35, also known as Nup53 in vertebrates, is a nucleoporin that is part of the nuclear pore complex (NPC). NPCs are gateways for transport between the nucleus and cytoplasm in eukaryotic cells, and Nup35 plays crucial roles in various biological processes such as nuclear transport, gene expression regulation, and nuclear envelope assembly [2]. It has been associated with pathways related to cell division, pH homeostasis, and viral entry [1,3,4]. Genetic models, especially mouse models, have been valuable in studying its functions.

In Caenorhabditis elegans, depletion of Nup35/NPP-19 inhibits NE localization of Nup155/NPP-8, NPC assembly, and nuclear lamina formation, leading to chromosome missegregation, nuclear morphology defects, and embryonic death around mid-gastrulation [2]. In mice, a point mutation in the RNA recognition motif of Nup35 causes a degenerative myopathy specifically affecting colonic smooth muscle, resulting in a severe megacolon and reduced lifespan, which may serve as a model for a subtype of chronic intestinal pseudo-obstruction (CIPO) [5]. In cardiomyocytes, Nup35 ablation weakens the resistance to an acid challenge by depressing the expression of Na⁺-H⁺ exchanger-1 (NHE1), as Nup35 regulates NHE1 expression by controlling the nucleo-cytoplasmic trafficking of nhe1 mRNA [3]. In oocytes, knockdown of Nup35 significantly compromises the extrusion of the first polar body, with defects in spindle assembly and chromosome alignment [4].

In conclusion, Nup35 is essential for nuclear assembly, cell division processes in embryos and oocytes, and pH homeostasis in cardiomyocytes. The study of Nup35 knockout or mutant mouse models has provided insights into its role in diseases such as CIPO and potential mechanisms underlying ischemic cardiac diseases, highlighting its significance in understanding biological functions and disease mechanisms [2,3,5].