In IPF, SPP1+ macrophages are highly expanded in fibrotic lesions and cross talk with myofibroblasts to drive fibrotic changes (Morse et al., 2019); in colorectal cancer, there are direct interactions between SPP1+ macrophages and FAP+ fibroblasts expressing high levels of MMP1/3 (Qi et al., 2022). The gene discussed is FAP; the disease is colorectal cancer.