A method of identifying compounds capable of modulating trans-glutaminase (TG) kinase activity is described. The method involves adding a test compound to a mixture of TG and a suitable TG kinase substrate, incubating the mixture under conditions promoting TG kinase activity, and determining if the test compound activates or modulates TG kinase activity as indicated by greater than expected TG-mediated phosphorylation of the TG kinase substrate or if the test compound inhibits TG kinase activity as indicated by lower than expected TG-mediated phosphorylation of the TG kinase substrate as compared to a control comprising TG and a suitable TG kinase substrate incubated under conditions promoting TG kinase activity.