The multifunctional or moonlighting protein CD26/DPPIV

CD26/DPPIV can be considered a moonlighting protein because it is a multifunctional protein that exerts its different functions depending on cell type and intra- or extracellular conditions in which it is expressed. In the present review, we summarize all its known functions in relation to physiological and pathophysiological conditions. The protein is a proteolytic enzyme, receptor, costimulatory protein, and is involved in adhesion and apoptosis. The CD26/DPPIV protein plays a major role in immune response. Abnormal expression is found in the case of autoimmune diseases, HIV-related diseases and cancer. Natural substrates for CD26/DPPIV are involved in immunomodulation, psycho/neuronal modulation and physiological processes in general. Therefore, targeting of CD26/ DPPIV and especially its proteolytic activity has many therapeutic potentials. On the other hand, there are homologous proteins with overlapping proteolytic activity, which thus may prevent specific modulation of CD26/DPPIV. In conclusion, CD26/DPPIV is a protein present both in various cellular compartments and extracellularly where it exerts different functions and thus is a true moonlighting protein.