Chmp4b, a core component of the endosomal sorting complex required for transport (ESCRT)-III, is essential for endosomal sorting and various membrane remodeling and scission processes in eukaryotes [4,5,6,7]. It is involved in pathways related to cell division, apoptosis, and membrane repair, and plays a crucial role in maintaining cell and tissue integrity [1,2,3,4,5,6]. Genetic models, such as KO/CKO mouse models, have been valuable in studying its functions.

In zebrafish, silencing of HSP90β, which directly interacts with Chmp4b, leads to up-regulation of Chmp4b, causing excessive division of lens epithelial cells, apoptosis via the p53/Bak-Bim pathway, and ultimately cataractogenesis [1]. In mouse models, homozygous germ-line mutations in Chmp4b are embryonic lethal, while conditional loss of Chmp4b results in arrest of lens growth and differentiation [7]. In the cockroach Blattella germanica, RNAi-mediated depletion of Chmp4b disrupts the integrity of follicular cells in the ovary, leading to female sterility [5]. In microglia after traumatic brain injury, overexpression of Chmp4b alleviates necroptosis, improves neurological function recovery, and protects against cell death [8].

In conclusion, Chmp4b is crucial for multiple biological processes, including cell division, differentiation, and membrane integrity maintenance. Studies using KO/CKO mouse models and other genetic manipulation methods in various organisms have revealed its significant roles in diseases such as cataractogenesis, endometrial carcinoma, Alzheimer's disease, and in the context of brain injury-related microglial responses. These findings contribute to a better understanding of the molecular mechanisms underlying these diseases and may offer potential therapeutic targets.