Using a variety of preclinical models of disease that feature neuroinflammation, including HIV-1-associated neurocognitive disorders (HAND) [14], Alzheimer’s disease (AD) [15, 16], and multiple sclerosis (MS) [17], we have demonstrated the therapeutic efficacy of the small-molecule, blood-brain barrier (BBB)-permeable, mixed-lineage kinase 3 (MLK3) inhibitor URMC-099 [15, 16]. Here, MAP3K11 is linked to multiple sclerosis.