BACKGROUND: Treatment of brain injuries and neurodegenerative disorders is a critical challenge due to poor regenerative capabilities of the central nervous system. The current therapeutic strategies are primarily focussed on treating the symptoms than addressing the core issue of loss of neurons. Despite advances in stem cell therapies and surgical alternatives, they are not always successful due to challenges like immune rejection and limited efficacy. Direct neuronal reprogramming of endogenous somatic cells is a promising approach to restore lost neurons. This review evaluates traditional reprogramming techniques and their limitations, explores novel DISCUSSION: Traditional neuronal reprogramming is based on CONCLUSIONS: Direct neuronal reprogramming offers a viable strategy for replenishing neuronal cell mass in neurodegenerative diseases and brain injuries through autologous therapy. Novel This article aims to explain direct neuronal reprogramming as focused treatment for the root causes of neurodegenerative diseases, replenishing lost neuronal cell mass.