This study investigates the role of telomere-related differentially expressed genes (TRDEGs) in intervertebral disc degeneration (IVDD) through comprehensive bioinformatics analyses. Data were sourced from the Gene Expression Omnibus (GEO) with datasets GSE245147 and GSE124272 used for initial identification and validation, respectively. The GSE245147 dataset comprised transcriptional profiles from nucleus pulposus cells of both degenerated and non-degenerated human nucleus pulposus (NP) tissues. Using the limma package, 198TRDEGs were identified by intersecting differentially expressed genes (DEGs) with telomere-related genes (TRGs) from the TelNet database. Functional enrichment analyses using the Database for Annotation, Visualization and Integrated Discovery (DAVID) revealed that TRDEGs are significantly involved in cell division, chromosome segregation, and other mitotic processes. Protein-protein interaction (PPI) networks constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and visualized with Cytoscape (Cytoscape Consortium, San Diego, CA, USA) identified key hub genes such as CDK1, CCNA2, and AURKB. Pearson correlation and receiver operating characteristic (ROC) analyses highlighted five hub genes (ASPM, BUB1B, CDC20, KIF2C, TTK) with significant predictive value for IVDD. Additionally, mRNA-microRNA (miRNA) interaction analysis using NetworkAnalyst identified key miRNAs interacting with these hub genes. This study provides insights into the molecular mechanisms of IVDD and identifies potential targets for therapeutic intervention.Copyright © 2024, Xie et al.