Canonically, NRF-1 is the major positive transcriptional regulator of CXCR4 while Ying Yang 1 is the negative transcriptional regulator, but other transcription factors also alter CXCR4 expression.15 PPARγ downregulates CXCR4 in cancer-associated fibroblasts.16 This is of particular interest because LRP1 can be cleaved by γ-secretase, translocate to the nucleus, and act as co-activator for PPARγ.14 Thus, it is possible that PPARγ is intermediary in regulation of CXCR4 by LRP1. The gene discussed is NRF1; the disease is cancer.