The EGFR subfamily of receptor tyrosine kinases is composed of EGFR, ErbB2, ErbB3 and ErbB4. The EGFR shares 43% - 44% aa sequence identity with the ECD of human EGFR subfamily. All these family members are type I transmembrane glycoproteins with an extracellular ligand binding domain. The extracellular ligand binding domain is containing two cysteine-rich domains separated by a spacer region and a cytoplasmic domain containing a membrane-proximal tyrosine kinase domain. Ligand binding could induce EGFR homodimerization and heterodimerization with ErbB2, resulting in cell signaling, heterodimerization tyrosine phosphorylation and kinase activation. It can bind EGF, amphiregulin, TGF-alpha, betacellulin, epiregulin, HB-EGF, epigen, and so on. Its signaling regulates multiple biological functions including cell proliferation, differentiation, motility, and apoptosis. EGFR can also be recruited to form heterodimers with the ligand-activated ErbB3 or ErbB4. EGFR is overexpressed in different tumors. Several anti-cancer drugs use EGFR as target.