MICB (MHC class I polypeptide-related sequence B) is a membrane-bound stress-inducible ligand that activates the NKG2D receptor on natural killer cells, γδ T cells, and CD8+ T cells 12. Upon cellular stress from viral/bacterial infection or DNA damage, MICB surface expression increases and engages NKG2D, triggering NK cell cytotoxicity and cytokine production 3. MICB expression is post-transcriptionally regulated by microRNAs binding to 5'- and 3'-UTR regions 4. Clinically, MICB is relevant in cancer immunology: tumors evade immune recognition through proteolytic shedding of MICB, and antibodies blocking this shedding or epitope-directed vaccines targeting the proteolytic region restore NK cell-mediated tumor immunity 35. In colorectal cancer, anti-MICB antibodies enhance tumor destruction by increasing NK cell infiltration and activation, with synergistic effects when combined with NKG2A blockade 6. Beyond cancer, MICB genetic variants contribute to systemic sclerosis (SSc) risk through dysregulation in fibroblasts and endothelial cells 7. MICB shows high genetic polymorphism across populations with population-specific allele frequency distributions 89, and its expression patterns across tissues suggest roles beyond classical immune surveillance 10.