Rnls, also known as renalase, is a multi-functional signaling molecule. It is a secretory protein with potent prosurvival and anti-inflammatory effects. Extracellularly, it signals through a specific plasma membrane calcium export transporter, while intracellularly, it functions as a FAD-dependent oxidoreductase (EC 1.6.3.5) [3,4].

In type 1 diabetes (T1D) mouse models, deleting Rnls via genome-scale CRISPR screen made beta cells resistant to autoimmune killing, suggesting Rnls as a modifier of beta cell vulnerability and a potential therapeutic target for T1D [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 peptide protected against CKD [2]. In melanoma models, Rnls knockout (KO) mice showed tumour rejection in a T-cell-dependent manner, and anti-Rnls antibody treatment enhanced T cell infiltration and activation in tumour-bearing mice [5].

In conclusion, Rnls plays crucial roles in multiple biological processes and disease conditions. Gene knockout models, especially in mice, have revealed its significance in diseases such as T1D, CKD, and melanoma, highlighting its potential as a therapeutic target for these diseases.