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 implicated in various cellular functions such as intracellular signaling, especially receptor tyrosine kinase (RTK)-mediated pathways [2]. It also plays a crucial role in cellular and systemic magnesium homeostasis, being involved in embryonic development, global ischemia, cardiovascular disease, and cancer [3]. Genetic models, like gene knockout in animal models, have been instrumental in uncovering its functions.

In the context of rheumatoid arthritis (RA), the expression of Trpm7 is elevated in articular chondrocytes from adjuvant arthritis (AA) rats and human RA patients. Knockdown or pharmacological inhibition of Trpm7 protects chondrocytes from ferroptosis, alleviating articular cartilage destruction in AA rats. This occurs via suppression of the PKCα-NOX4 axis, suggesting Trpm7-mediated chondrocyte ferroptosis as a potential target for RA treatment [1]. In ovarian cancer, its overexpression is linked to adverse prognostic outcomes, promoting cancer invasion, metastasis, and cell proliferation [4]. In neurodevelopment, global knockout of Trpm7 or Trpm7-kinase is embryonically lethal, and it is involved in key neurodevelopmental processes. Discrepancies in its expression are associated with neuropathological conditions [5].

In conclusion, Trpm7 is essential for multiple biological functions including magnesium homeostasis, cellular signaling, and is involved in various disease conditions such as RA, ovarian cancer, and neurodegenerative diseases. The use of gene knockout and other genetic models has been pivotal in revealing its role in these processes, providing potential therapeutic targets for these diseases.