CLIC5, or Chloride Intracellular Channel 5, belongs to the chloride intracellular channel protein family. It has been implicated in multiple physiological processes. It can exist in both soluble and integral membrane forms, with the transmembrane form showing ion-channel activity in vitro [2]. CLIC5 is involved in pathways like the canonical Wnt/β-catenin signaling pathway, and is important for myogenesis, skeletal muscle regeneration, and maintaining normal systemic energy metabolism [1,3]. Genetic models, such as KO mouse models, have been crucial in studying its functions.

Deletion of CLIC5 in skeletal muscle leads to reduced muscle weight, decreased satellite cell number and differentiation potential. In vitro, it inhibits myoblast proliferation and promotes myotube formation, functioning through a BGN-dependent activation of the canonical Wnt/β-catenin signaling pathway [1]. CLIC5 mutant mice are lean, hyperphagic, and resistant to diet-induced obesity, but show gastric hemorrhaging, immune and neurological dysfunctions, and increased susceptibility to torpor, revealing its role in maintaining normal systemic energy metabolism [3].

In conclusion, CLIC5 is a key regulator in myogenesis and muscle regeneration via the BGN-mediated Wnt/β-catenin pathway, and is also essential for normal systemic energy metabolism. Studies using CLIC5 KO mouse models have provided valuable insights into its functions in these biological processes, which could potentially contribute to understanding related disease mechanisms such as muscle regeneration disorders and metabolic diseases.