Nogo, so named as a “No-Go” for neurite outgrowth, is a member of the reticulon family of transmembrane proteins, and is also called reticulon 4 (gene name RTN4) (1-4). Reticulons lack N-terminal signal sequences, share a conserved ~200 amino acid (aa) C-terminus that contains two transmembrane domains and an ER‑retention motif, and show a punctate intracellular distribution within the endoplasmic reticulum (ER) that is reminescent of a reticulum (1-3). The N-terminus of intracellular (ER) Nogo-A appears to face the cytoplasm (1-3). However, minor amounts of Nogo-A and Nogo-B are found in the plasma membrane with extracellular N-termini (4-6). Full length rat Nogo-A is a 1163 aa protein with a long (~989 aa) N-terminus that includes bioactive regions (aa 59-172 and 544-725), a transmembrane segment, a connecting loop that contains the bioactive Nogo-66 region, a second transmembrane segment, and a short C-terminus (3). The four Nogo isoforms share the Nogo66 segment, Nogo-A and Nogo-B share aa 1-172, and only Nogo-A contains aa 544-725 (1-3). Rat Nogo-A shares 78% and 91% aa sequence identity with human and mouse Nogo-A, respectively. Rat and human Nogo-A/B also share 78% aa sequence identity within aa 1-172 and 98% within the Nogo-66 loop region. Nogo-A is mainly expressed in oligodendrocytes of the central nervous system, but is also reported in fibroblasts, dorsal root ganglion neurons, macrophages and myoblasts (1-8). Nogo-B is mainly expressed in vascular endothelium and smooth muscle throughout the body (1, 4, 6, 9). The Nogo66 region binds the GPI-linked Nogo receptor/p75 complex on axons, inducing growth cone collapse (5, 7, 10, 11). Either aa 59-172 or 544-725 segments can block neurite outgrowth and fibroblast spreading (5, 6). Nogo-A/B aa 1-172 is also reported to regulate vascular remodeling through binding the Nogo-B receptor (NgBR/NUS1) on vascular cells, and to inhibit neuronal differentiation and promote glial formation from neural progenitors (4, 5, 8, 9, 12).