Polymerase-1 and release transcript factor (PTRF) was initially reported to be involved in the termination of the transcription process. More recently, it has been implicated in the formation of caveolae, cave-like structures in the plasma membrane. The effects of PTRF related to caveolae suggest that this protein may play important roles in health and disease. PTRF is highly expressed in various cells, including adipocytes, osteoblasts and muscle (cardiac, skeletal and smooth) cells. The role of PTRF in prostate cancer has been recently reviewed but there is growing evidence that PTRF is involved in other physiological processes such as cell repair and the regulation of glucose and lipid metabolism and, furthermore, altered expression of PTRF may be associated with disease. This review discusses the emerging role of PTRF in health and disease.