Well-studied examples of such genes are RASAL1 (which encodes for a Ras-GAP-like Ras-GTP inhibitor, and hypermethylation of the RASAL1 promoter leads to silencing of RASAL1 expression and increased RAS-GTP activity)4–6 and KL1 (which encodes for Klotho, a transmembrane protein working as a co-receptor for fibroblast growth factor-23), both of which have been associated with cancer and also fibrogenesis:7–11 The RASAL1 promoter is consistently hypermethylated in tissue fibrosis including kidney, heart, and liver and also in gastrointestinal cancers4–6,9,13. The gene discussed is KL; the disease is cancer.