[Objective] To elucidate the signal sensing logic of the three-component EsrISR system, which is composed of the accessory protein EsrI, the histidine kinase EsrS, and the response regulator EsrR, in Corynebacterium glutamicum under hyperosmotic stress and its molecular mechanism for maintaining cell wall homeostasis. [Methods] The core stress-responsive gene cluster was identified through RNA-seq. A series of deletion mutants and overexpression strains were constructed through homologous recombination technology. The transcriptional fusion reporter system, field emission scanning electron microscopy/transmission electron microscopy (FESEM/TEM), electrophoretic mobility shift assay (EMSA), and real-time quantitative reverse transcription PCR, (RT-qPCR) were employed to systematically investigate the sensing threshold, stress response patterns, and global target gene networks of this system. [Results] RNA-seq showed that the esrISR gene cluster was significantly upregulated under 1.7 mol/L NaCl stress. Under the same stress conditions, the deletion of the regulator EsrR led to a significant decrease in biomass, with the maximum OD₆₀₀ dropping to 47.8% of that of the wild type. Moreover, severe damage and collapse of the cell wall were observed via electron microscopy. The construction and analysis of reporter plasmids showed that this system was driven by an internal promoter, peaking at 1.7 mol/L NaCl, with a maximum fluorescence intensity of 880 RFU/OD₆₀₀. The proposed regulatory model indicated that in the absence of external stress, EsrS mainly exerted phosphatase activity to repress the transcription of esrI, thereby maintaining the repressed state of the system (deletion of esrS led to an approximately 15.0-fold upregulation of esrI). Upon sensing hyperosmotic signals, EsrS changed its activity, promoting the phosphorylation of the regulator EsrR. Subsequently, the phosphorylated EsrR specifically bound to the core regulatory region, thereby activating the positive feedback regulatory loop. Transcriptomic analysis revealed significant alterations in the expression of key genes associated with cell wall homeostasis in the esrR deletion mutant (ΔesrR). RT-qPCR analysis confirmed that EsrR functioned as a crucial regulator of cell wall biosynthesis primarily by positively activating key pathway genes. Specifically, the peptidoglycan synthesis genes murB and CGL_RS01830 were downregulated by 95.0% in ΔesrR and upregulated by 2.0-6.5 fold in esrR-OE; the trehalose biosynthesis genes treS, treY, and treZ were downregulated by 75.0%-83.0% in ΔesrR and upregulated by 2.5-4.2 fold in esrR-OE; cmrA and gatC were significantly repressed in ΔesrR and upregulated by 3.5-folds in esrR-OE, thereby effectively maintaining the physical homeostasis of the cell wall. [Conclusion] This study provides new insights into the regulation of cell wall homeostasis by the three-component EsrISR system in Corynebacterium, providing critical genetic targets for the robustness engineering of industrial chassis strains.