Reticulon-4 receptor-like 2

Reticulon-4 receptor-like 2 (RTN4RL2) is a cell surface receptor that mediates inhibition of neurite outgrowth and plays a role in developmental axon migration and corpus callosum formation (UniProt: Q86UN3). The protein contributes to synapse and dendritic spine regulation during brain development through Rho signaling and actin cytoskeleton reorganization, and provides neuroprotection against motoneuron apoptosis.

RTN4RL2 is expressed in the developing and mature central nervous system, where it functions redundantly with other family members in axonal development and synaptic refinement (UniProt: Q86UN3). The protein does not appear to significantly regulate axon regeneration in the adult brain.

RTN4RL2 is down-regulated in Alzheimer's disease brain tissue compared to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of −0.475 across two of four subcellular fractions examined in post-mortem tissue. This reduction may reflect diminished synaptic maintenance or developmental signaling capacity in AD pathology.