ANKRD22 is a nuclear-encoded mitochondrial membrane protein with context-dependent roles in immune regulation and cancer progression. In immune cells, ANKRD22 functions as a negative regulator of inflammation. It suppresses PMN-MDSC immunosuppressive activity by regulating CCR2 expression and glucose uptake 1, and promotes psoriasiform inflammation resolution by antagonizing NIK-mediated IL-23 production through direct NIK binding and degradation 2. In colon cancer, elevated ANKRD22 in M1-type tumor-associated macrophages correlates with improved patient survival and proinflammatory activity 3. Conversely, ANKRD22 exhibits oncogenic functions in solid tumors: it promotes glioma progression via E2F1-mediated MELK upregulation 4, NSCLC advancement through E2F1 transcriptional regulation 5, and nasopharyngeal carcinoma via m6A-dependent ANKRD22 stabilization that enhances lipid metabolism and creates a positive feedback loop with METTL14 6. ANKRD22 regulates mitochondrial Ca2+ homeostasis and promotes gastric mucosal repair through Wnt/β-catenin pathway activation 7. Clinically, elevated serum ANKRD22 independently predicts drug-resistant tuberculosis 8. These findings establish ANKRD22 as a promising therapeutic target across multiple diseases, with potential ANKRD22-activating or -upregulating compounds showing therapeutic promise.