The article discusses the clinical progression of Parkinson's disease (PD) and the neurobiology of axons, highlighting the importance of axon degeneration in the disease process. Despite significant advancements in understanding PD's molecular basis and cell injury pathways, effective therapies to halt disease progression remain elusive. The authors argue that axon degeneration, rather than cell body degeneration, may be the primary driver of clinical progression. They propose that early involvement of axons in PD is underappreciated in current therapeutic strategies and suggest that focusing on axon degeneration could lead to novel therapeutic targets. The article reviews evidence from animal models and genetic studies, including the role of α-synuclein and LRRK2 mutations, to support this hypothesis. It also discusses the distinct molecular mechanisms of axon and soma degeneration, emphasizing the need for therapeutic approaches that target axonal pathology. The authors conclude by advocating for a greater emphasis on axon neurobiology in PD research and therapy development, suggesting that preserving axonal integrity could be a more realistic and effective therapeutic goal.The article discusses the clinical progression of Parkinson's disease (PD) and the neurobiology of axons, highlighting the importance of axon degeneration in the disease process. Despite significant advancements in understanding PD's molecular basis and cell injury pathways, effective therapies to halt disease progression remain elusive. The authors argue that axon degeneration, rather than cell body degeneration, may be the primary driver of clinical progression. They propose that early involvement of axons in PD is underappreciated in current therapeutic strategies and suggest that focusing on axon degeneration could lead to novel therapeutic targets. The article reviews evidence from animal models and genetic studies, including the role of α-synuclein and LRRK2 mutations, to support this hypothesis. It also discusses the distinct molecular mechanisms of axon and soma degeneration, emphasizing the need for therapeutic approaches that target axonal pathology. The authors conclude by advocating for a greater emphasis on axon neurobiology in PD research and therapy development, suggesting that preserving axonal integrity could be a more realistic and effective therapeutic goal.