LRRC15, also known as LIB and hLib, is a leucine-rich repeat-containing protein that is highly expressed in various solid tumors. It is found on stromal fibroblasts in many solid tumors, including those of the breast, head and neck, lung, and pancreas, as well as directly on a subset of cancer cells of mesenchymal origin, such as sarcoma, melanoma, and glioblastoma. LRRC15 expression can be induced by TGFβ in activated fibroblasts (positive for α-smooth muscle actin, αSMA) and in mesenchymal stem cells. These collective findings suggest that LRRC15 serves as a novel cancer-associated fibroblast (CAF) and mesenchymal marker, making it a potential therapeutic target for the treatment of cancers with LRRC15-positive stromal desmoplasia or those of mesenchymal origin.