Sec13, as a component of the coat protein complex II (COPII), the nuclear pore complex (NPC), and the Seh1-associated (SEA)/GATOR nutrient-sensing complex, plays crucial roles in protein trafficking from the endoplasmic reticulum to the Golgi apparatus, NPC functions, and nutrient-sensing pathways [2,5]. It is also involved in processes like cellular metabolism, growth, and immune regulation [3,4]. Genetic models, such as gene-knockout models, are valuable for studying its functions.

In oligodendrocyte (OL) lineage cells, ablation of Sec13 prevented OPC differentiation, inhibited myelination and remyelination after demyelinating injury in the central nervous system (CNS), as it altered the secretome of OLs and inhibited the secretion of pleiotrophin (PTN), an autocrine factor for OL differentiation and myelin repair [1]. In zebrafish, a sec13(sq198) mutant with a carboxyl-terminus-truncated Sec13 that lost affinity to Sec31a led to ER structure disintegration in various differentiated cells, activating an unfolded protein response, cell-cycle arrest, and apoptosis, ultimately arresting the growth of developing digestive organs [6]. In mice with low-level Sec13 expression (Sec13(H/-)), specific immunological defects were observed, including low levels of MHC I and II in macrophages, low INF-γ and IL-6 in stimulated T cells, and high levels of TGF-β, indicating Sec13 as a negative modulator of TGF-β expression [4].

In conclusion, Sec13 is essential for multiple biological processes. Its role in OL differentiation and myelination, as well as in maintaining ER integrity during organogenesis and regulating immune factors, has been revealed through model-based research. The Sec13 KO/CKO mouse models contribute to understanding diseases related to demyelination, organ development, and immune-related disorders.