SPP1 is secreted in various cancers, including PTCs, to drive invasion, metastasis, and therapy resistance.[21] We observed that SPP1hi‐Macro engaged ligand‐receptor pairs (SPP1‐ITGA5/ITGB1/CD44) with PTC or endothelial cells to enhance communication (Figure S6, Supporting Information), suggesting a functional role in PPTC. Here, SPP1 is linked to cancer.