Sec23b, encoding SEC23 homologue B, is a component of coat protein complex II (COPII), which canonically transports proteins from the endoplasmic reticulum (ER) to the Golgi [5]. This function is crucial for various cellular processes, including autophagy and the regulation of membrane protein glycosylation, and is involved in maintaining normal cell function in different tissues [2,3]. Genetic models, such as gene knockout mouse models, have been instrumental in studying Sec23b's role.

In SEC23B-deficient mice, germline absence leads to perinatal death with pancreatic degeneration, indicating its essential role in pancreatic acinar cell function in adult mice [4]. Moreover, SEC23B-deficient mice lacking all four Sec23 alleles (erythroid-specific deletion) die in mid-embryogenesis with features of congenital dyserythropoietic anemia type II (CDAII), while those with three allele deletions show a milder erythroid defect [1]. In human cells, SEC23B-deficient HUDEP-2 cells exhibit CDAII features upon differentiation, which can be rescued by increased SEC23A expression [1]. In hepatic cells, loss-of-function of SEC23B impairs the glycosylation pathway, suppressing hepcidin expression and contributing to hepatic iron overload in CDAII [2].

In conclusion, Sec23b is essential for normal protein transport via the COPII complex, influencing processes in multiple tissues. The study of Sec23b using gene knockout mouse models has revealed its crucial role in diseases like CDAII, especially in relation to ineffective erythropoiesis and iron overload, providing insights into the disease mechanisms and potential therapeutic strategies.