Folr2, the folate receptor 2, is one of the folate transporters and is known to be involved in folate-related processes. Folates are B vitamins crucial for one-carbon metabolism, and Folr2's role in this context may have implications for various cellular functions [6].

Folr2-expressing macrophages have been identified in multiple disease-related contexts. In breast cancer, FOLR2+ tissue-resident macrophages localize in perivascular areas of the tumor stroma, interact with CD8+ T cells, and their density positively correlates with better patient survival, suggesting a role in antitumor immunity [1]. In hepatocellular carcinoma, there is a re-emergence of fetal-like (FOLR2) tumor-associated macrophages as part of an onco-fetal reprogramming of the tumor microenvironment [2]. In chronic kidney disease, CXCL-iFibro fibroblasts promote the switch of macrophages into FOLR2+ macrophages, and this interaction is involved in fibrosis progression [3]. In colon cancer, a subset of FOLR2+ macrophages is embedded in plasma cell niches [4]. In gastric cancer, FOLR2+ macrophages possess antitumor immune potential, but their proportion decreases during the progression from intestinal metaplasia to early gastric cancer [5]. In lung adenocarcinoma, FOLR2-expressing tumor-associated macrophages may be involved in the formation of an immunosuppressive microenvironment through a trajectory related to regulatory T cells [7]. Also, TIM4+FOLR2+ macrophages in tertiary lymphoid structures across several cancer types are associated with an active immune infiltrate, and the TIM4+FOLR2+ macrophage subsets have different prognostic implications [8].

In conclusion, Folr2, through its association with macrophages, plays diverse roles in cancer and chronic kidney disease. In cancers, it can either be associated with promoting antitumor immunity or contributing to immunosuppressive microenvironments. In chronic kidney disease, it is involved in the fibrotic process. The study of Folr2 in these disease conditions helps in understanding the underlying immune-related and disease-progression mechanisms, potentially providing new therapeutic targets.