The misinterpreted boundary: Clarifying the unique attributes of the cartilaginous endplate and its central mechanism in intervertebral disc degeneration

Abstract: The intervertebral disc (IVD) is a complex structure vital for spinal function, whose degeneration is a leading cause of low back pain. While research has traditionally focused on the nucleus pulposus (NP) and annulus fibrosus (AF), the cartilaginous endplate (CEP)—the critical interface between the disc and vertebral body—has been historically underappreciated and often anatomically conflated with the adjacent bony endplate (BEP). This review aims to systematically synthesize current knowledge to clarify the unique attributes of the CEP and establish its role as the primary initiator of the IVD degenerative cascade. We first elucidate the fundamental biology of the CEP, distinguishing its distinct histological identity and dual “mechanical and nutritional” functions, which are essential for disc homeostasis. Subsequently, we detail the morphological progression and functional consequences of CEP degeneration, emphasizing its strong clinical relevance to discogenic pain and treatment outcomes. A core section critically examines the mechanisms of degeneration, focusing on the traditional “nutrient deprivation hypothesis” linked to reduced CEP permeability and a newer perspective highlighting the paramount importance of CEP–BEP interfacial integrity as a potential initiator of pathological cascades. We then evaluate the characteristics and limitations of various animal models used in CEP research, providing guidance for model selection based on specific scientific questions. Furthermore, we summarize recent advances in the molecular and cellular mechanisms driving CEP degeneration, including dysregulated matrix metabolism, aberrant mechanotransduction, oxidative stress, and epigenetic regulation. In conclusion, this review positions the CEP not as a passive structure but as an active hub whose health dictates IVD fate. Recognizing CEP degeneration as a pivotal driver offers significant translational relevance, shifting the clinical focus toward early-stage diagnosis and disease-modifying therapeutic strategies. Future interventions targeting CEP matrix health and interfacial integrity hold the potential to halt or reverse disc degeneration at its source, providing a paradigm shift in the management of chronic low back pain.