PRPH (peripherin) is a class-III neuronal intermediate filament protein primarily expressed in the peripheral nervous system that functions as a structural component of the neuronal cytoskeleton 1. PRPH can form independent filamentous networks or cooperate with other neurofilament proteins (NEFL, NEFH, NEFM, and INA) to establish the cytoskeletal architecture essential for axonal integrity 2. The gene contains conserved regulatory elements including nerve growth factor response elements and heat shock elements, suggesting tissue- and injury-specific expression control 2. PRPH plays critical roles in peripheral nervous system development, axon elongation, and regeneration following injury, while paradoxically inhibiting neurite extension in cochlear spiral ganglion neurons 3. Recent evidence indicates PRPH serves as an early biomarker for motor neuron disease; plasma PRPH levels are significantly elevated in amyotrophic lateral sclerosis (ALS) and other motor neuron diseases, correlating with disease progression and survival 4. PRPH also emerges as a biomarker for traumatic axonal injury, with elevated levels in cerebrospinal fluid and plasma following traumatic brain injury, reflecting cytoskeletal damage 5. Changes in PRPH mRNA transport in peripheral nerves have been observed in diabetic peripheral neuropathy, suggesting perturbations in axonal RNA localization contribute to neurodegeneration 6. These findings position PRPH as both structurally essential and clinically relevant for diagnosing and prognosticating neurodegenerative pathologies.