The p75 neurotrophin receptor (p75NTR) was first identified in 1973 as the low-affinity nerve growth factor receptor (LNGFR) before discovery that p75NTR bound other neurotrophins equally well as nerve growth factor. p75NTR is a neurotrophic factor receptor. Neurotrophic factor receptors bind Neurotrophins including Nerve growth factor, Neurotrophin-3, Brain-derived neurotrophic factor, and Neurotrophin-4. All neurotrophins bind to p75NTR. This also includes the immature pro-neurotrophin forms. Neurotrophic factor receptors, including p75NTR, are responsible for ensuring a proper density to target ratio of developing neurons, refining broader maps in development into precise connections. p75NTR is involved in pathways that promote neuronal survival and neuronal death. Receptor family p75NTR is a member of the tumor necrosis factor receptor superfamily. p75NTR/LNGFR was the first member of this large family of receptors to be characterized, that now contains about 25 receptors, including tumor necrosis factor 1 (TNFR1) and TNFR2, Fas, RANK, and CD40. All members of the TNFR superfamily contain structurally related cysteine-rich modules in their ECDs. p75NTR is an unusual member of this family due to its propensity to dimerize rather than trimerize, because of its ability to act as a tyrosine kinase co-receptor, and because the neurotrophins are structurally unrelated to the ligands, which typically bind TNFR family members. Indeed, with the exception of p75NTR, essentially all members of the TNFR family preferentially bind structurally related trimeric Type II transmembrane ligands, members of the TNF ligand superfamily. Structure p75NTR is a type I transmembrane protein, with a molecular weight of 75 kDa, determined by glycosylation through both N- and O-linkages in the extracellular domain. It consists of an extracellular domain, a transmembrane domain and an intracellular domain. The extracellular domain consists of a stalk domain connecting the transmembrane domain and four cysteine-rich repeat domains, CRD1, CRD2, CRD3, and CRD4; which are negatively charged, a property that facilitates Neurotrophin binding. The intracellular part is a global-like domain, known as a death domain, which consists of two sets of perpendicular helixes arranged in sets of three. It connects the transmembrane domain through a flexible linker region N-terminal domain. It is important to say that, in contrast to the type I death domain found in other TNFR proteins, the type II intracellular death domain of p75NTR does nor self-associated. This was an early indication that p75NTR does nor signal death through the same mechanism as the TNFR death domains, although the ability of the p75NTR death domain