In this review, we will describe the metabolism of GnRH to generate GnRH-(1–5), provide a brief overview on the discovery of its bioactivity, and discuss how the biological responses elicited by GnRH-(1–5) in endometrial cancer cells are mediated by GPR101 to stimulate cell growth and metastatic behavior. The gene discussed is GNRH1; the disease is endometrial cancer.