The proteasome, the principal intracellular protein-degradation system, is essential for nerve regeneration after injury.This review summarizes recent evidence that the proteasome orchestrates axonal regeneration by modulating growth-cone formation, microtubule dynamics, reactive oxygen species (ROS) levels, and neuroinflammation. Proteasomes are delivered to growth cones via retrograde axonal transport, and their localization and activity depend on neuronal maturation and axon length.They further promote growth-cone assembly and axonal extension by regulating tubulin expression and polymerization.As key signaling molecules, ROS levels are tightly coupled to proteasome activity; their reciprocal interactions fine-tune axonal regrowth. Notably, immunoproteasome subunits such as PSMB5i contribute to neurodegeneration via inflammatory pathways. In a cohort of 316 ischemic stroke patients, plasma levels of LMP2, MECL-1, and LMP7 were markedly elevated in the 13.3 % who developed hemorrhagic transformation (P < 0.05), suggesting their utility as early biomarkers of stroke complications. Elucidating these proteasome-driven mechanisms in both regeneration and pathology will inform novel therapeutic strategies for neural repair and related disorders.