TMP21 is a ubiquitously expressed protein that is involved in vesicular targeting and protein transport.  More recent experiments have shown that it is also a component in the presenilin complex and modulates the gamma-secretase but not the epsilon-secretase cleavage activity of the amyloid precursor protein.  The presenilin complex is composed of the proteins APH1, nicastrin, and PEN2 in addition to presenilin-1.  Together, these proteins cleave the amyloid precursor protein at what is known as the gamma- and epsilon-sites and can lead to the accumulation of the Abeta cleavage product that is associated with Alzheimer’s disease. Co-immunoprecipitation experiments using antibodies against these proteins also yielded TMP21 indicating that TMP21 may play a role in the regulation of this complex.  Suppression of TMP21 expression by siRNA in transfected cells caused increased gamma-secretase activity but not epsilon-secretase activity, and increased Abeta; production, demonstrating that TMP21 can modulate gamma-secretase activity.