Fbxl22, or F-box and leucine-rich protein 22, is an E3 ubiquitin ligase. It is involved in regulating protein turnover, especially of sarcomeric proteins like α-actinin and filamin C, which is crucial for maintaining normal contractile function in cardiac and skeletal muscles. It may also be associated with pathways related to muscle atrophy, heart regeneration, and potentially breast cancer [2,3,4]. Genetic models such as zebrafish and mice are valuable for studying its functions.

In zebrafish, blocking AP-1 function leads to decreased chromatin accessibility at the fbxl22 locus, which is related to sarcomere disassembly during heart regeneration [1]. In mouse studies, overexpression of Fbxl22 isoforms in skeletal muscle causes myopathy/atrophy, indicating its role in neurogenic muscle atrophy. Moreover, knockdown of Fbxl22 in MuRF1 KO mice muscles shows additive muscle-sparing effects after denervation [2]. In rat cardiomyocytes and zebrafish embryos, targeted knockdown of Fbxl22 results in the accumulation of α-actinin, severely impaired contractile function, and cardiomyopathy [3].

In conclusion, Fbxl22 is essential for maintaining muscle contractile function through regulating sarcomeric protein degradation. Studies using gene-knockdown and overexpression models in mice and zebrafish have revealed its significance in muscle-related diseases such as muscle atrophy and cardiomyopathy, providing insights into potential therapeutic strategies for these conditions.