SMAD2 is an intracellular protein belonging to the Dwarfin (DWA/B)/SMAD family. SMAD2 associates with SMAD4 for translocation to the nucleus. It acts as an intracellular mediator of the TGFβ family of cytokines and activin type 1 receptor (ACVR1C). Hence it regulates multiple cellular processes like cell growth, proliferation, differentiation, and apoptosis and also cooperates with transcription factors to regulate expression of defined genes. Apart from playing an important role in TGFβ1-induced CTGF expression, SMADs also act as markers of epithelial-mesenchymal transition. SMAD2 also acts as an integrator of multiple signals in the regulation of NOS3 expression. It is ubiquitously expressed in most of tissues and may contribute to colorectal, hepatocellular, lung, and breast carcinomas as well as cervical cancer.