Rc3h1, also known as ROQUIN, is an RNA-binding protein and E3 ubiquitin ligase. It plays a crucial role in post-transcriptional regulation of mRNAs, participating in pathways such as the IKK/NF-κB pathway, and is important for maintaining immune homeostasis [2,3]. Genetic models like knockout mice are valuable for studying its functions.

In osteoclasts, Rc3h1-deficient mice exhibit low bone mass and enhanced osteoclast activation. Mechanistically, Rc3h1 post-transcriptionally represses Tfr1 expression, limiting iron absorption and mitochondrial respiration in osteoclasts. Inhibiting Tfr1 in Rc3h1-deficient osteoclasts reduces excessive osteoclast formation and mitochondrial respiration, suggesting the Rc3h1/Tfr1 axis could be a therapeutic target for bone-loss diseases [1]. In T cells, inactivation of Roquin-1 by MALT1 cleavage leads to spontaneous T cell activation and autoimmunity, while making Roquin-1 insensitive to MALT1 cleavage in Rc3h1Mins/Mins mice restores normal immune homeostasis [4].

In conclusion, Rc3h1 is a multifunctional regulator. Its functions include post-transcriptional regulation of mRNAs, which is crucial for immune homeostasis and bone metabolism. The study of Rc3h1 using gene-knockout mouse models has provided insights into its role in bone-loss diseases and autoimmunity, offering potential therapeutic directions for these conditions.