[3] The exact biochemical activity of transglutaminases was discovered in blood coagulation protein factor XIII in 1968.

The core domain belongs to the papain-like protease superfamily (CA clan) and uses a Cys-His-Asp catalytic triad.

The catalytic reaction is generally viewed as being irreversible, and must be closely monitored through extensive control mechanisms.

[2] Deficiency of factor XIII (a rare genetic condition) predisposes to hemorrhage; concentrated enzyme can be used to correct the abnormality and reduce bleeding risk.

[2] Anti-transglutaminase antibodies are found in celiac disease and may play a role in the small bowel damage in response to dietary gliadin that characterises this condition.

[2] In the related condition dermatitis herpetiformis, in which small bowel changes are often found and which responds to dietary exclusion of gliadin-containing wheat products, epidermal transglutaminase is the predominant autoantigen.

[14] Thrombin–fibrinogen "meat glue" from bovine and porcine sources was banned throughout the European Union as a food additive in 2010.