Abstract: Neurodevelopmental processes represent a finely tuned interplay between genetic and environmental factors, shaping the dynamic landscape of the developing brain. A major component of the developing brain that enables this dynamic is the white matter (WM), known to be affected in neurodevelopmental disorders (NDDs) (Rokach et al., 2024). WM formation is mediated by myelination, a multifactorial process driven by neuro-glia interactions dependent on proper neuronal functionality (Simons and Trajkovic, 2006). Another key aspect of neurodevelopmental abnormalities involves neuronal dynamics and function, with recent advances significantly enhancing our understanding of both neuronal and glial mitochondrial function (Devine and Kittler, 2018; Rojas-Charry et al., 2021). Energy homeostasis in neurons, attributed largely to mitochondrial function, is critical for proper functionality and interactions with oligodendrocytes (OLs), the cells forming myelin in the brain’s WM. We herein discuss the interplay between these processes and speculate on potential dysfunction in NDDs.