RTN4R (reticulon 4 receptor) is a cell surface receptor localized to the plasma membrane and neuronal structures that regulates neurite outgrowth and neural development 1. The receptor functions as a high-affinity ligand for brain-specific angiogenesis inhibitor (BAI) adhesion-GPCRs through its leucine-rich repeat domain, with binding enabled by unusual post-translational modifications including C-mannosylation and O-fucosylation 1. RTN4R mediates differential effects on dendritic arborization, axonal elongation, and synapse formation through interactions with glial versus neuronal BAI proteins 1. In vascular biology, RTN4R functions within an RTN4-S1PR2 signaling axis that negatively regulates angiogenesis and secondary neural repair following cerebral infarction by enhancing vascular autophagy through ROCK1-BECN1 interactions 2. RTN4R also regulates ataxin-2 protein levels, with RTN4R knockdown reducing ataxin-2 and promoting axonal regeneration 3. Disease relevance includes schizophrenia, with RTN4R mapping to the 22q11.2 susceptibility locus 4, though genetic studies show weak or absent association with schizophrenia in most populations 456. RTN4R also associates with impaired glucose tolerance risk 7 and represents a therapeutic target for amyotrophic lateral sclerosis and spinocerebellar ataxia type 2 3.