 Neurodegeneration is a common feature of many debilitating and incurable diseases, such as Parkinson's disease, which are rapidly increasing in prevalence. There is an urgent need to develop new and effective therapeutic strategies to combat these devastating diseases. Models, including cell-based systems, unicellular organisms, and complex animals, have proven useful in shedding light on the mechanisms underlying neurodegenerative diseases and providing promising therapeutic avenues. This themed issue of disease models and mechanisms features a collection of original research articles that provide new insights into the pathophysiology of such diseases, revealing candidate biomarkers or therapeutic targets. Some articles describe new disease models that enable deeper exploration of key mechanisms. Reviews highlight recent translational advances made in studies of neurodegenerative diseases. Model-based studies have had a significant impact on this exciting area of research, providing valuable insights into the complex pathophysiology of neurodegenerative diseases and paving the way for the development of new therapeutic strategies. This article was authored by Aaron D. Gitler, Paraminder Dhillon, and James Shorter. We are article.tv, links in the description below.