The Role of Neuritin 1 in Synaptic Plasticity and Sensory Nerve Function: Integrator of Neurotrophic, Metabolic and Injury Signals

Neuritin 1 (NRN1) has emerged as a multifaceted regulator of synaptic plasticity, neuronal excitability and structural remodelling. This review synthesises knowledge of NRN1 function across the central and peripheral nervous systems, with a focus on its roles in sensory neurones and neuronal repair following injury. We discuss evidence that NRN1 interacts with classical neurotrophic pathways, including brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), while engaging distinct cellular mechanisms that span activity-dependent trafficking, modulation of calcium and potassium channel function and regulated local axonal mRNA translation. Accumulating data indicate that NRN1 contributes to injury-induced plasticity and functional recovery through both cell-autonomous neuronal mechanisms and non-cell-autonomous signalling involving glial and stromal cells. In long-projecting sensory axons, regulated transport and local translation of Nrn1 mRNA position NRN1 as a spatially restricted effector of axonal growth, excitability and regeneration. Dysregulation of NRN1 expression and signalling has been implicated in pathological contexts including neurodegeneration, diabetic peripheral neuropathy and inflammatory pain, where restoration of NRN1 activity promotes axonal integrity, Schwann cell survival and neurotrophic support. Beyond neurons, NRN1 also modulates inflammatory and angiogenic pathways, including VEGF and CXCR4 signalling, linking neuronal plasticity to broader tissue and immune responses. Together, these findings support a model in which NRN1 acts as a molecular integrator of neurotrophic, metabolic and injury-associated signals, coordinating plasticity while also presenting potential routes to maladaptive sensitisation. We highlight key mechanistic and translational challenges that must be addressed to harness NRN1 biology therapeutically aimed at enhancing neuronal repair while limiting persistent sensory dysfunction.