Although several details are still missing, the biological role of two of the three well characterized transglutaminases in mammals, namely blood coagulation factor XIII and keratinocyte transglutaminase, is established. The function of the third one called the tissue type is still an enigma. Its constant localization in endothelial and smooth muscle cells of all organs, in heart muscle, in medullary interstitial and mesangial cells of kidney, and its induction in a number of other cell types under a variety of conditions suggest multiple functions. According to our results its participation in the biochemical pathway leading to programmed cell death (apoptosis), a basic cellular phenomenon of physiological significance, may be one of these functions.