Fat for thought: Lipid regulation of neural stem cell fate

Lipids are increasingly recognized as critical regulators of neurogenesis and neural differentiation, with functions that extend beyond their well-known roles as structural membrane components or energy substrates. Evidence demonstrates that specific lipid species and their bioactive derivatives modulate neural stem cell behavior, influencing proliferation, lineage specification, and maturation. These effects are mediated through multiple mechanisms, including activation of lipid-responsive nuclear receptors, remodeling of membrane microdomains, and metabolic reprogramming of progenitor cells. In addition, interactions between lipids and lipid-binding proteins or enzymes that control lipid turnover have emerged as central nodes governing neuronal fate decisions. Within the neurogenic niches of the developing and adult brain, dynamic alterations in lipid composition shape cellular behavior, and perturbations in lipid signaling are increasingly associated with neurodevelopmental and neuropsychiatric disorders. Here, we review recent advances elucidating how lipids orchestrate neurogenesis and neural differentiation and explore the therapeutic potential of targeting lipid pathways to promote brain repair and modulate disease.