BRAF^V600E vs. cell of origin: what governs LCH? Shi and colleagues performed Immunophenotyping and singlecell RNA sequencing to identify differentially expressed genes in circulating mononuclear cells from pediatric patients with Langerhans cell histiocytosis. Summarized are their key findings on the effect of the BRAF^V600E mutation on gene expression in various cell populations, and the effect of treatment with BRAF inhibitor on differential gene expression.