Ischemia has been shown to upregulate OPG expression,[177] and elevated plasma levels of OPG are associated with poor prognosis in ischemic stroke.[178] Inhibition of OPG expression has been linked to, suggesting that increased OPG may contribute to decreased RANKL/RANK signaling and heightened post‐ischemic inflammation.[177] Conversely, OPG signaling may exert neuroprotective effects in multiple sclerosis by reducing inflammation through the downregulation of RANKL/RANK activity.[179] The interplay between neurons and glial cells further complicates the role of OPG in the CNS. This evidence concerns the gene TNFRSF11A and ischemic stroke.