MACIR (macrophage immunometabolism regulator) is a 206 amino acid disordered protein that regulates macrophage function and inflammatory resolution. Primary function: MACIR enhances M2 macrophage-mediated wound repair and resolution of inflammation by inhibiting glycolysis 1. Mechanistically, MACIR interacts with nuclear transport receptor TNPO1 via a non-classical proline/tyrosine-nuclear localization signal motif and with trafficking proteins UNC119A/B, suggesting roles in protein trafficking and potentially ciliary membrane localization 2. Disease relevance: MACIR expression inversely correlates with rheumatoid arthritis disease activity and synovial TNF expression 1. Loss of MACIR function increases fibroblast migration and invasion, upregulating genes involved in cell migration, adhesion, angiogenesis, and inflammatory pathways 3. MACIR expression is significantly reduced in periodontitis gingival tissue, where inflammatory cytokines IL-1β and TNF-α suppress its expression 4. Clinical significance: MACIR functions as a negative regulator of tissue damage; its inhibition markedly accentuates joint inflammation in collagen-induced arthritis models 3. The rs26232 variant in the C5orf30 locus (MACIR's former designation) associates with radiologic severity of joint damage in RA 5, establishing MACIR as therapeutically relevant for autoimmune and inflammatory diseases.