Chmp5, or Charged multivesicular body protein 5, is a member of the multivesicular body and the endosomal-sorting complex required for transport (ESCRT) [3,4]. It is essential for late endosome function, down-regulating receptor signaling, and controlling membrane-scission events in eukaryotic cells [3,4]. CHMP5 is also involved in multiple pathways, such as the NF-κB pathway, and is of great biological importance in processes like embryogenesis, bone turnover, and immune cell function [2,3]. Genetic models, especially KO/CKO mouse models, have been crucial in studying its functions.

In a Chmp5-deficient mouse model, deletion of CHMP5 in osteoclasts led to increased bone resorption by osteoclasts and exuberant bone formation by osteoblasts, resembling human Paget's disease of bone. This was due to increased RANKL-induced NF-κB activation and osteoclast differentiation in CHMP5-deficient osteoclasts [2]. In the context of osteoarthritis, proteomics identified downregulated CHMP5 in OA patient cartilages. Overexpression of CHMP5 repressed chondrocyte apoptosis and extracellular matrix degradation in OA chondrocytes, while silencing CHMP5 exacerbated these effects, with the protective effect involving the NF-κB signaling pathway [1].

In conclusion, CHMP5 plays essential roles in multiple biological processes, especially those related to endosome function and signaling pathway regulation. The use of KO/CKO mouse models has significantly contributed to understanding its role in diseases such as Paget's-like skeletal disorders and osteoarthritis, providing potential therapeutic targets for these diseases.