PTBP1: A master regulator of neural development and transdifferentiation-promise and pitfalls

The polypyrimidine tract-binding protein 1 (PTBP1), a pivotal RNA-binding protein and splicing regulator, is emerging as a master orchestrator of neuronal fate determination, neurodevelopment, and neural function through its central role in alternative splicing. We synthesize current knowledge on PTBP1's multifaceted roles in orchestrating neural tube formation, neuronal migration, and synaptic circuit assembly through precise control of alternative splicing programs. We critically examine the rapidly evolving field of PTBP1-mediated cellular reprogramming, analyzing both supportive evidence and significant controversies surrounding glia-to-neuron conversion across species. We further integrate molecular mechanisms with pathophysiological relevance, highlighting how PTBP1 dysregulation contributes to neurodevelopmental disorders and neurodegenerative conditions including Alzheimer's and Parkinson's diseases. We evaluate emerging therapeutic strategies targeting PTBP1, assessing their mechanistic foundations, technical limitations, and translational potential. Crucially, we highlight key methodological considerations and species-specific regulatory differences that must be addressed to realize PTBP1's therapeutic promise. This synthesis provides a critical framework for future research directions at the intersection of RNA biology, neural development, and regenerative neuroscience.