RYK (receptor tyrosine kinase) functions as a WNT-binding receptor with dual roles in neuronal development and metabolic disease. As a coreceptor with FZD8 for WNT ligands including WNT1, WNT3, WNT3A, and WNT5A, RYK mediates multiple developmental processes through non-canonical Wnt signaling pathways 1. In the nervous system, RYK exhibits context-dependent functions: during embryonic development, Wnt5a/Ryk signaling provides essential chemorepulsive guidance for axon navigation, particularly in establishing the corticospinal tract and corpus callosum 2. Upon WNT3 stimulation, RYK undergoes proteolytic cleavage in its transmembrane region, releasing a C-terminal fragment that translocates to the nucleus to regulate neuronal development 3. After spinal cord injury, astrocyte-specific Ryk expression coordinates wound healing and scar formation; Ryk knockout elongates reactive astrocytes and accelerates border formation while reducing scar size 4. Recently, RYK was identified as a functional receptor for the GPNMB ectodomain (G-ECD), where G-ECD/RYK interaction activates ERK1/2 signaling and promotes hepatic lipid uptake and lipogenesis through PPARγ-CD36 and SREBP1C pathways, driving metabolic-dysfunction-associated steatohepatitis (MASH) progression 5. These findings establish RYK as a multifunctional receptor with therapeutic potential in neurological injury and metabolic disease.