Trpm7, short for transient receptor potential melastatin-subfamily member 7, is a ubiquitously expressed chanzyme. It has an ion channel permeable to divalent cations like Mg2+, Ca2+, and Zn2+, and an α-kinase that phosphorylates downstream substrates. It is involved in various cellular functions and intracellular signaling, especially receptor tyrosine kinase (RTK)-mediated pathways [2]. TRPM7 is crucial for cellular and systemic magnesium homeostasis and thus plays a key role in embryonic development, cardiovascular disease, cancer, and other (patho)physiological processes [3]. Genetic models, such as gene knockout (KO) mouse models, have been vital in understanding its functions.

In rheumatoid arthritis, knockdown or pharmacological inhibition of TRPM7 protected chondrocytes from ferroptosis. Adeno-associated virus 9-mediated TRPM7 silencing or its blockade alleviated articular cartilage destruction in adjuvant arthritis rats, suggesting it as a potential target for RA treatment [1]. In cancer, overexpression of TRPM7 is linked to adverse prognostic outcomes. It promotes cancer invasion, metastasis, and cell proliferation. For example, in ovarian cancer, it controls the calcium ion signaling and metabolic reprogramming pathways [4]. Genetic inactivation of TRPM7 in animal models has uncovered its critical role in early embryonic development, immune responses, and organismal ion balance, with malfunctions associated with anoxic neuronal death, tissue fibrosis, tumour progression, etc. [5].

In conclusion, Trpm7 is essential for maintaining cellular ion homeostasis and regulating multiple intracellular signaling pathways. Model-based research, especially through KO mouse models, has revealed its significant roles in diseases like rheumatoid arthritis and cancer. Understanding Trpm7 functions provides potential therapeutic targets for these and other diseases associated with its malfunction.