Beyond the connection with CNS, FBXO3 has been demonstrated to mediate ubiquitination degradation of F-Box and Leucine Rich Repeat Protein 2 (FBXL2) [14], thereby promoting inflammatory cytokines’ expression [15] and rescuing the expression of NLR Family Pyrin Domain Containing 3 (NLRP3) [16], which has been confirmed to prompt inflammatory cascade and neuronal damage in ischemic stroke [17,18]. The gene discussed is FBXL2; the disease is ischemic stroke.