Elucidation of the mechanism by which receptor tyrosine kinases (RTKs) modulate cellular physiology in response to stimuli is critical to the understanding of growth regulation, as miscues in RTK signaling can result in cellular transformation events that may ultimately lead to cancer. Eps15 (EGF-receptor pathway substrate 15) is an EGF receptor substrate that become become tyrosine phosphorylated subsequent to EGF stimulation. Over expression of Eps15 in NIH/3T3 cells causes cellular transformation, implying involvement of Eps15 in the regulation of cell proliferation. Eps15R (Eps15-related), also known as Eps15L1 (epidermal growth factor receptor substrate 15-like 1), is an 864 amino acid protein that contains one EF-hand domain and three EH domains. Localized to a variety of places within the cell, including the nucleus, cytoplasm and membrane-coated pits, Eps15R is thought to function as a component of clathrin-coated pits. Like Eps15, Eps15R may play an important role in receptor-mediated endocytosis.