Rnls, also known as renalase, is a multi-functional signaling molecule. It is a secretory protein with prosurvival and anti-inflammatory effects. It can regulate cell signaling both extracellularly and potentially intracellularly. Extracellularly, it signals through a specific plasma membrane calcium export transporter. Its functions are relevant to various biological processes and diseases [3].

In type 1 diabetes (T1D) mouse models, deleting Rnls made beta cells resistant to autoimmune killing, suggesting it as a modifier of beta cell vulnerability and a potential therapeutic target [1]. In cisplatin-induced chronic kidney disease (CKD) mouse models, genetic deletion of Rnls was associated with more severe CKD, and kidney-targeted delivery of a Rnls agonist protected against CKD [2]. In melanoma models, Rnls knockout mice could reject their tumours in a T-cell-dependent manner, and anti-Rnls antibody treatment enhanced anti-PD-1 activity [4].

In conclusion, Rnls plays essential roles in maintaining cell survival, inflammation regulation, and immunity. Studies using gene knockout mouse models have revealed its significance in diseases such as T1D, CKD, and melanoma, providing potential therapeutic directions for these diseases.