Calsyntenin-2 (CS-2) is a 120-135kD member of the Alcadein family of molecules. It is expressed in the ER/Golgi, and the plasma membranes of almost all neurons. It is a calcium-binding protein that interacts with APP and X11L. In this regard, it appears to regulate APP cleavage and gene activation, and likely impacts post-synaptic signaling. Notably, when cleaved in a manner similar to APP, its intracellular fragment antagonizes AICD gene activation. Mature human CS-2 is a 935aa type I transmembrane protein. It contains two cadherin domains aa44-280 in its extracellular region aa21-831 and a 103aa cytoplasmic tail. Proteolytic cleavage by ADAM10 occurs between His803 and Leu804 to generate a 105-110kD extracellular fragment. Additional processing of the transmembrane fragment by g-secretase creates a 3kD fragment aa804-834 plus a 25kD cytoplasmic protein. Potential isoform variants show a premature truncation after Gln608, and the use of an alternative start site at Met409. Over aa21-834, human CS-2 shares 95aa identity with mouse CST-2.