Rnls, also known as renalase, is a multi-functional signaling molecule. It is a secretory protein with prosurvival and anti-inflammatory effects. Extracellularly, it signals through a specific plasma membrane calcium export transporter, while intracellularly, it is a FAD-dependent oxidoreductase [3,5]. It is involved in various biological processes and has potential implications in multiple diseases, making it an important target for functional studies.

In a mouse model for type 1 diabetes (T1D), genome-scale CRISPR screen showed that deleting RNLS made beta cells resistant to autoimmune killing, identifying it 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, while kidney-targeted delivery of a RNLS agonist peptide protected against CKD by decreasing cell death and improving the viability of the renal proximal tubule [2]. In melanoma models, RNLS knockout (KO) mice injected with wild-type melanoma cells rejected their tumours, and anti-RNLS antibody treatment enhanced T cell infiltration and activation, suggesting RNLS inhibition promotes tumour rejection [4].

In conclusion, Rnls plays crucial roles in protecting beta cells in T1D, preventing cisplatin-induced CKD, and influencing tumour rejection in melanoma. Gene knockout mouse models have been instrumental in revealing these functions, providing insights into potential therapeutic strategies for these disease areas.