CD28 (Cluster of Differentiation 28) is a homodimeric stimulatory cell surface receptor of the immunoglobulin (Ig) superfamily that is located on the chromosome 2q33.2. It is expressed on naive T cells and has also been found on the surface of plasma cells, eosinophils, and neutrophils. CD28 remains the most extensively studied costimulatory molecular and is a primary one for T-cell activatio. The control of T-cell responses through CD28 co-stimulation provides a means of anti-self and antimicrobial immunity. CD28 is essential for the lymphocyte activation and survival. A number of antigen-experienced T-cells lose CD28, and then can be re-activated without its engagement. Diseases linked to CD28 involve mycosis fungoides and Sezary's disease and the related pathways are Th2 differentiation pathway and RET signaling. The EPCAM gene provides an instruction for the protein named epithelial cellular adhesion molecule. It is a type I membrane protein of 314 amino acids in humans, which consists of a large extracellular domain (N-terminal) of 242 amino acids, a short cytoplasmic domain of 26 amino acids (C-terminal) and a single-spanning transmembrane domain of 23 amino acids. The encoded EPCAM gene is located on the chromosome 2p21 and estimated with a size of 14 kb. This transmembrane glycoprotein with approximately 35kDa mediates Ca2+-independent homotypic cell-cell adhesion in epithelial cells and responses to cell surface interactions at the vascular wall. Diseases linked to EPCAM include congenital and colorectal cancer, with tufting enteropathy, and so on. It is used as a target for immunotherapy treatments of human cancer.