In this disease model, Siglec-15 plays a role as a “ligand” for an unknown inhibitory receptor on cytotoxic T cells, in much the same way as PD-L1 (aka B7-H1, CD274) on cancer cells or tumor stroma engages immune checkpoint molecule PD-1 on T cells (Fig. 1b) [45–47]. The gene discussed is CD274; the disease is cancer.