Researchers in the 1960s investigating brown adipose tissue, found that in addition to producing more heat than typical of other tissues, brown adipose tissue seemed to short circuit, or uncouple, respiration coupling. Uncoupling protein 1 was discovered in 1976 by David G. Nicholls, Vibeke Bernson, and Gillian Heaton, and the discovery was published in 1978 and shown to be the protein responsible for this uncoupling effect. UCP1 was later purified for the first time in 1980 and was first cloned in 1988.
Uncoupling protein two (UCP2), a homolog of UCP1, was identified in 1997. UCP2 localizes to a wide variety of tissues, and is thought to be involved in regulating reactive oxygen species (ROS). In the past decade, three additional homologs of UCP1 have been identified, including UCP3, UCP4, and UCP5 (also known as BMCP1 or SLC25A14).