Slc22a17, also known as the neutrophil gelatinase-associated lipocalin/lipocalin-2 (LCN2)/24p3 receptor, is an atypical member of the SLC22 family. It doesn't transport typical SLC22 substrates but mediates receptor-mediated endocytosis (RME) of LCN2. It is involved in multiple biological processes such as iron-handling, protein reabsorption in the kidney, and regulation of tight junctions. It may also play a role in the tumor microenvironment and is linked to various disease-related pathways [2,3,4,5,7].

In cerebral ischemia, in vivo experiments using mouse models of transient focal cerebral ischemia and in vitro experiments with human brain endothelial cultures showed that SLC22A17 may play a role in controlling blood-brain barrier (BBB) function. Endothelial expression of SLC22A17 increases with BBB leakage after cerebral ischemia. Short interfering RNA against SLC22A17 prevents TNF-α-induced ferroptosis, down-regulation of tight junction proteins, and disruption of transcellular permeability in human brain endothelial cultures, and also ameliorates BBB leakage in mouse models of focal cerebral ischemia [1]. In macrophages, Slc22a17 knockdown reduced MMP9 release when treated with recombinant LCN2, suggesting its role in the macrophage-mediated response post-myocardial infarction [6].

In conclusion, Slc22a17 has essential functions in processes like iron metabolism, protein reabsorption, and tight-junction regulation. Gene-knockout studies, especially in mouse models, have revealed its significance in diseases such as cerebral ischemia and myocardial infarction, providing insights into potential therapeutic targets for these conditions.