FOLR2 (folate receptor beta) functions as a high-affinity folate binding protein that mediates cellular uptake of folate and reduced folic acid derivatives through receptor-mediated endocytosis. Beyond its canonical role in folate transport, FOLR2 serves as a critical marker for distinct macrophage populations across tissues. FOLR2+ macrophages represent tissue-resident macrophages that are maintained through self-renewal with minimal monocyte input and are among the first to emerge developmentally from yolk sac precursors 1. These FOLR2+ macrophages exhibit conserved transcriptional signatures across tissues and between mouse and human 1. In cancer contexts, FOLR2+ macrophages demonstrate complex roles depending on tissue and spatial localization. In breast cancer, FOLR2+ macrophages localize to perivascular areas, interact with CD8+ T cells, and correlate with better patient survival 2. However, in ovarian and triple-negative breast cancers, FOLR2-expressing macrophages correlate with poor clinical outcomes 3. In hepatocellular carcinoma, FOLR2+ macrophages are part of an onco-fetal reprogramming signature associated with immunosuppression and tumor progression 4 5. The spatial segregation of FOLR2+ macrophages in distinct microenvironmental niches, including plasma cell-rich areas, suggests specialized functional roles that impact cancer prognosis 6.