Intervertebral disc (IVD) degeneration is a leading contributor to chronic low back pain, a condition with significant socioeconomic and healthcare burdens worldwide. Despite its prevalence, early diagnosis and effective, targeted therapies for IVD degeneration remain limited, largely due to an incomplete understanding of the molecular mechanisms underlying disease onset and progression. Traditionally, research has focused on the local disc environment, but emerging evidence suggests that systemic factors — particularly those circulating in the bloodstream — may play a critical role in disc homeostasis and degeneration. The plasma proteome, representing a dynamic collection of circulating proteins, offers a powerful window into systemic physiological states. Advances in high-throughput proteomics now make it possible to detect subtle yet biologically significant shifts in circulating protein profiles, potentially unveiling biomarkers indicative of tissue-specific changes, including those occurring in the intervertebral disc. However, the systemic proteomic landscape associated with IVD degeneration remains underexplored. This project aims to leverage plasma proteomics to uncover systemic protein biomarkers linked to IVD degeneration. By comparing the plasma profiles of individuals with varying degrees of disc degeneration to those of healthy controls, we seek to identify protein signatures reflective of disc pathology. These findings could not only improve early detection and monitoring strategies but also provide novel insights into systemic contributors to disc disease, paving the way for more personalized and effective therapeutic approaches.