Small leucine-rich proteoglycans (SLRPs) play an essential role in extracellular matrix (ECM) organization and function. Recently, dysregulation of SLRPs has been implicated in degenerative disc disease (DDD). An in-depth analysis using high-throughput proteomic sequencing might provide valuable information on their implications in health and disease. Hence we utilized proteomics for analysing the expression of SLRPs in fetal, healthy adult, and degenerated discs to identify possible molecular targets to halt or reverse the degenerative process.