Human Meissner Corpuscles: From Classical Morphology to Molecular Mechanobiology and Clinical Significance

Meissner corpuscles are specialized cutaneous mechanosensory end organs primarily located in the dermal papillae of human glabrous skin and specialized mucocutaneous territories. Traditionally regarded as rapidly adapting tactile receptors composed of a sensory axon surrounded by passive lamellar cells, current evidence supports a more complex organization in which the axon, terminal glial cells (TGCs), extracellular matrix, and endoneurial capsule form an integrated mechanosensory unit. This review provides an updated synthesis of the development, anatomical distribution, structural organization, molecular phenotype, mechanotransduction, functional neurobiology, aging, and pathological alterations of human Meissner corpuscles. Particular attention is given to the molecular identity of TGCs and to their emerging role as active components of corpuscular function. PIEZO2 remains the best-established mediator of primary mechanotransduction in the sensory axon, whereas human TGCs express several mechanosensing-associated proteins and experimental evidence suggests a potential glial contribution to corpuscular function. Human studies also demonstrate substantial regional and age-related variability in corpuscular density and phenotype. Importantly, Meissner corpuscles undergo quantitative, structural, immunophenotypic, and molecular alterations in a broad spectrum of peripheral and central neurological disorders. Recent evidence of disease-associated molecular pathology, including intracorpuscular phosphorylated TDP-43 in amyotrophic lateral sclerosis, further expands their potential relevance as accessible peripheral indicators of neurological disease. Finally, emerging three-dimensional imaging, tissue-clearing, spatial molecular profiling, functional imaging, and quantitative digital approaches provide new opportunities for investigating human corpuscular organization. Collectively, current evidence supports viewing the Meissner corpuscle as a dynamic neuro-glial mechanosensory organ whose biological and clinical significance extends beyond its classical role in discriminative touch.