Since little is known about the factors involved in the regulation or in the recruitment of telomere-binding proteins to telomeres during normal development and in pathological conditions, our current findings demonstrating how the nuclear function of HRG unexpectedly involves the alteration of telomere homeostasis via TRF2 and RAP1, adds a further tier of complexity to the regulatory mechanisms of telomere length and function during tumor initiation and metastasis. The gene discussed is TERF2IP; the disease is neoplasm.