Member of the repulsive guidance molecule (RGM) family that performs several functions in the developing and adult nervous system. Regulates cephalic neural tube closure, inhibits neurite outgrowth and cortical neuron branching, and the formation of mature synapses. Binding to its receptor NEO1/neogenin induces activation of RHOA-ROCK1/Rho-kinase signaling pathway through UNC5B-ARHGEF12/LARG-PTK2/FAK1 cascade, leading to collapse of the neuronal growth cone and neurite outgrowth inhibition. Furthermore, RGMA binding to NEO1/neogenin leads to HRAS inactivation by influencing HRAS-PTK2/FAK1-AKT1 pathway. It also functions as a bone morphogenetic protein (BMP) coreceptor that may signal through SMAD1, SMAD5, and SMAD8. Interacts with NEO1, BMP2 and BMP4. Expressed in gradient in periventricular layers of the developing nervous system. In adult, expressed in scattered cells throughout the brain. Expressed in the early developing nervous system, with the exception of prominent gaps in the mid-hindbrain and the fore-midbrain boundaries. By 10.5 dpc, expression in the nervous system decreases slightly and a segmented pattern of expression appears, marking the ventral sites of somitic buds. At that stage, the expression shows a strong dorsal to ventral gradient. In the neural tubes, strong expression is detected at the level of the floor plate and in the medial portion of the neural tubes. Lower expression is detected in the dorsal neural tube and the ventral aspect corresponding to the area of motoneuron differentiation. In the developing eye, expressed in the perioptic mesenchyme. Autocatalytically cleaved at low pH; the two chains remain linked via two disulfide bonds. Belongs to the repulsive guidance molecule (RGM) family.