Human epidermal growth factor (EGF), also known as urogastrone (URG) since it was isolated from urine based on its inhibitory effect on gastric secretion, is the founding member of the EGF-family of growth factors. All the members of this protein family have highly similar structural and functional characteristics. EGF is initially synthesized as a 130 kDa single-pass transmembrane protein containing 9 EGF-like units and 9 LDL-receptor class B repeats. The mature soluble EGF is a 6 kDa peptide corresponding to the EGF unit located proximal to the transmembrane domain. EGF is expressed in kidney, salivary gland, cerebrum and prostate, and plays an important role in the regulation of cell growth, proliferation, and differentiation by binding to its receptor EGFR. As a potent mitogen, EGF stimulates the growth of various epidermal and epithelial tissues both in vivo and in vitro. Furthermore, EGF is also identified as a magnesiotropic hormone that stimulates magnesium reabsorption in the renal distal convoluted tubule via engagement of EGFR and activation of the magnesium channel TRPM6. Defects in EGF are the cause of hypomagnesemia type 4 (HOMG4), a disorder characterized by massive renal hypomagnesemia and normal levels of serum calcium and calcium excretion.