Gdnf, short for glial cell line-derived neurotrophic factor, is a 134-amino-acid protein belonging to the GDNF family ligands (GFLs) [2]. It plays a crucial role in the survival, maintenance, and regeneration of specific neuronal populations in the adult brain. Gdnf can trigger receptor tyrosine kinase RET phosphorylation, activating several intracellular signaling pathways that are essential for the development, survival, and maintenance of neuron-neuron and neuron-target tissue interactions [2]. It is involved in the development of the enteric nervous system, kidney, lower urinary tract, and spermatogenesis [4].

In the context of neurodegenerative diseases, Gdnf has been investigated as a potential therapeutic option. In Parkinson's disease, initial clinical trials showed promise, with Gdnf administration being considered an effective treatment, but subsequent double-blind, placebo-controlled trials did not achieve the primary end-point [1,3]. There are also concerns about cerebellar toxicity after continuous intraputamenal high-dose administration in rhesus monkeys [6]. In pancreatic cancer, exosomal lncRNA XIST promotes perineural invasion by increasing the release of Gdnf from neural cells [5].

In conclusion, Gdnf is vital for the normal development and function of the nervous system and other organs. Its role in neurodegenerative diseases like Parkinson's disease and cancer-related processes such as pancreatic cancer perineural invasion has been explored through various research models. However, challenges remain in translating its potential therapeutic benefits into successful clinical treatments.