Through in silico gene perturbation modeling, an animal knockout model, and in vitro culture assays, we validated the function of candidate genes and proteins within disease‐associated cell subpopulations.[10] Our results consolidated the role of ILB+ macrophages (Mφs) in driving the progression of disc degeneration and identified LCN2high MDSCs and LCN2 as novel immunomodulatory treatment targets attenuating IVDD. This evidence concerns the gene LCN2 and intervertebral disk degenerative disorder.