The Leptin receptor is a member of the Class I cytokine receptor family. It mediates the activities of Leptin, a multi-functional hormone produced primarily by adipose tissues that plays roles in food intake, energy metabolism, angiogenesis, reproduction, hematopoiesis, bone metabolism, and immune function. The human Leptin R gene encodes 1165 amino acids (aa) including a signal peptide, an extracellular region with cytokine receptor homology (CRH), multiple fibronectin type III domains and a WSXWS motif, a transmembrane domain, and a cytoplasmic domain that supports JAK/STAT signaling. Soluble Leptin R is the primary Leptin-binding protein in blood, where it maintains a pool of available bioactive Leptin, delays Leptin clearance from circulation, and down-regulates blood-brain transmission of Leptin. In humans, soluble Leptin R levels are inversely proportional to adiposity and are elevated in females versus males. Soluble Leptin R is also found up-regulated in patients with chronic heart failure, end-stage renal disease, and anorexia.It is expressed by tumor-initiating stem cells, and is proposed as a link between cancer and obesity.