Background: EPS15 is involved in cell growth regulation, possibly via the regulation of mitogenic signals and control of cell proliferation. EPS15 also participates in the internalization of ligand-inducible receptors of the receptor tyrosine kinase (RTK) type, in particular EGFR. Potential interaction partners include AP2A2, STN2, EPN1, and CRK via its SH3-binding sites. EPS15 is ubiquitously expressed. Phosphorylation on Tyr-849 is involved in the internalization of EGFR. EPS15 is not required for membrane translocation after EGF treatment or for targeting to coated pits, but essential for a subsequent step in EGFR endocytosis. This protein is involved in a t(1,11)(p32,q23) chromosomal translocation in acute leukemias causing fusion to the trithorax (MLL or HRX) gene product which contains DNA-binding motifs resulting in a rogue activator protein. Structurally, EPS15 contains 2 EF-hand calcium-binding domains, 3 EH domains, and 2 ubiquitin-interacting motif (UIM) repeats.