Required to induce the formation and stabilization of endoplasmic reticulum (ER) tubules. They regulate membrane morphogenesis in the ER by promoting tubular ER production. They influence nuclear envelope expansion, nuclear pore complex formation and proper localization of inner nuclear membrane proteins. However each isoform have specific functions mainly depending on their tissue expression specificities. Developmental neurite growth regulatory factor with a role as a negative regulator of axon-axon adhesion and growth, and as a facilitator of neurite branching. Regulates neurite fasciculation, branching and extension in the developing nervous system. Involved in down-regulation of growth, stabilization of wiring and restriction of plasticity in the adult CNS (PubMed:12037567, PubMed:12843238, PubMed:20573699). Regulates the radial migration of cortical neurons via an RTN4R-LINGO1 containing receptor complex. Acts as a negative regulator of central nervous system angiogenesis. Inhibits spreading, migration and sprouting of primary brain microvascular endothelial cells (MVECs). Also induces the retraction of MVECs lamellipodia and filopodia in a ROCK pathway-dependent manner (By similarity). Mainly function in endothelial cells and vascular smooth muscle cells, is also involved in immune system regulation (By similarity). Modulator of vascular remodeling, promotes the migration of endothelial cells but inhibits the migration of vascular smooth muscle cells. Regulates endothelial sphingolipid biosynthesis with direct effects on vascular function and blood pressure. Inhibits serine palmitoyltransferase, SPTLC1, the rate-limiting enzyme of the novo sphingolipid biosynthetic pathway, thereby controlling production of endothelial sphingosine-1-phosphate (S1P). Required to promote macrophage homing and functions such as cytokine/chemokine gene expression involved in angiogenesis, arteriogenesis and tissue repair. Mediates ICAM1 induced transendothelial migration of leukocytes such as monocytes and neutrophils and acute inflammation. Necessary for immune responses triggered by nucleic acid sensing TLRs, such as TLR9, is required for proper TLR9 location to endolysosomes. Also involved in immune response to LPS. Plays a role in liver regeneration through the modulation of hepatocytes proliferation (By similarity). Reduces the anti-apoptotic activity of Bcl-xl and Bcl-2. This is likely consecutive to their change in subcellular location, from the mitochondria to the endoplasmic reticulum, after binding and sequestration. With isoform C, inhibits BACE1 activity and amyloid precursor protein processing (By similarity). Regulates cardiomyocyte apoptosis upon hypoxic conditions (By similarity). With isoform B, inhibits BACE1 activity and amyloid precursor protein processing (By similarity). Binds to RTN4R (By similarity). Interacts with ATL1 (PubMed:19665976). Interacts with TMEM170A (By similarity). Interacts with RTN4IP1 (By similarity). Interacts in trans with CNTNAP1 (PubMed:14592966). Interacts with REEP5 (By similarity). Homodimer (By similarity). Interacts with BAD/Bcl-xl and BCL2. Interact with RTN3 (By similarity). Interacts with NGBR (By similarity). Interacts with SPTLC1 (By similarity). Interacts with GRAMD4 (By similarity). Interacts with CDH5 (By similarity). Interacts with BACE1 and BACE2 (By similarity). Interacts with REEP5 (By similarity). Interacts with BACE1 and BACE2 (By similarity). Interacts with TMEM33 (By similarity). Anchored to the membrane of the endoplasmic reticulum (ER) through 2 putative transmembrane domains. Localizes throughout the ER tubular network. Co-localizes with TMEM33 at the ER sheets. Mainly located on endoplasmic reticulum tubules and sheet edges. Upon ICAM1 engagement, redistributed toward endothelial junctions where interacts with CDH5. Isoforms A, B and C are present in optic nerve, spinal cord and cerebral cortex. Isoforms A and B are present in dorsal root ganglion, sciatic nerve and PC12 cells after longer exposure. Isoforms B and C are detected in kidney, cartilage, skin, lung and spleen. Isoform C is expressed at high level in skeletal muscle. In adult animals isoform A is expressed mainly in the nervous system. Three regions, residues 59-172, 544-725 and the loop 66 amino acids, between the two transmembrane domains, known as Nogo-66 loop, appear to be responsible for the inhibitory effect on neurite outgrowth and the spreading of neurons. This Nogo-66 loop, mediates also the binding of RTN4 to its receptor. N-terminal part, called Am-Nogo-B(1-200), is the functional domain for RTN4B-mediated signaling in endothelial and vascular smooth muscle cells. Nerve regrowth: nipped by a no-go - Issue 69 of April 2006