CDNF (cerebral dopamine neurotrophic factor) is an unconventional neurotrophic factor that primarily functions as an endoplasmic reticulum (ER) luminal protein involved in cellular stress response and neuroprotection 1. Unlike classical neurotrophic factors, CDNF lacks cell surface receptors and instead localizes mainly in the ER cavity, where it regulates ER stress and the unfolded protein response (UPR) 2. The protein contains a unique structure with a saposin-like N-terminal domain and a C-terminal KDEL retrieval sequence that maintains its ER localization 3. CDNF demonstrates significant neuroprotective and neurorestorative effects on midbrain dopaminergic neurons, making it a promising therapeutic candidate for Parkinson's disease 4. In preclinical models, CDNF protects against dopaminergic neurodegeneration, reduces neuroinflammation by decreasing IL-1β and C3 levels, and modulates ER stress markers including CHOP and GRP78 5. Beyond its neuroprotective functions, CDNF suppresses protein aggregation and inflammation, and can directly interact with alpha-synuclein 3. CDNF has successfully completed Phase I-II clinical trials for Parkinson's disease, demonstrating safety and tolerability 4. The protein's expression is regulated by specific microRNAs including miR-134 and miR-141 6.