The sortilin family of Vps10p-domain receptors includes sortilin, SorLA, and SorCS1-3. These type-I transmembrane receptors predominate in distinct neuronal tissues, but expression is also present in certain specialized non-neuronal cell populations including hepatocytes and cells of the immune system. The biology of sortilins is complex as they participate in both cell signaling and in intracellular protein sorting. Sortilins function physiologically in signaling by pro- and mature neurotrophins in neuronal viability and functionality. Recent genome-wide association studies have linked members to neurological disorders such as Alzheimer's disease and bipolar disorder and outside the nervous system to development of coronary artery disease and type-2 diabetes. Particularly well described are the receptor functions in neuronal signaling by pro- (proNT) and mature (NT) neurotrophins and in the processing/metabolism of amyloid precursor protein (APP).