The Cribriform Plate: A Multifaceted Neuroimmune Hub in CNS Health and Disease

The cribriform plate (CP) functions as a dynamic neuroimmune interface through which olfactory nerve bundles exit the brain within a specialized perineural microenvironment (cpPME). While traditionally viewed as a passive structural barrier, emerging evidence positions the CP as a central hub for cerebrospinal fluid (CSF) drainage, glymphatic–lymphatic clearance, and antigen presentation. This review provides a comprehensive understanding of recent advances in cpPME research, highlighting the adaptive remodeling of the immune landscape in response to neuroinflammation and aging. We critically evaluate the translational gap between rodent models and human physiology, discussing the implications for neurodegenerative diagnostics, neuroinflammatory conditions, infectious diseases and “nose-to-brain” therapeutic delivery. By integrating anatomical, physiological, and immunological perspectives, we offer a comprehensive framework for understanding the CP’s role in CNS homeostasis and its potential as a transformative diagnostic and therapeutic target.