While earlier reports have inferred the functions of SPHK1/S1P axis in promoting the growth, tumorigenicity and metastasis of ER-positive breast CSCs, recent evidence has further highlighted that the activation of SPHK1/S1P axis is greater in CSCs than non-stem cancer cells across different subtypes of breast cancers (Hii et al., 2020). The gene discussed is MBTPS1; the disease is cancer.