Rare genetic conditions affecting brain development are often difficult to diagnose, especially when the responsible gene has previously been studied only in adult brain diseases. In this study, we describe two siblings with a severe neurodevelopmental disorder caused by a loss-of-function change in the TTBK1 gene. TTBK1 is best known for its role in Alzheimer’s disease and other neurodegenerative conditions, but its importance during early brain development has been unclear. Our findings provide the first human evidence that TTBK1 is essential for normal motor and cognitive development. This work expands the list of genes causing childhood neurodevelopmental disorders and highlights how genes linked to adult brain diseases can also play critical roles early in life. (By Zehra Manav Yigit, MD, https://jmg.bmj.com/content/early/2026/01/15/jmg-2025-111208 )