This study explores why some children are born with very small head size (microcephaly) due to rare changes in the CDK4 or CDK6 genes. These genes normally help cells divide and grow. We found that when they do not work properly, cells struggle to multiply and instead become stressed. Rather than simply slowing down, the cells activate their energy-producing structures in an unusual way, leading to damage and cell death. This helps explain how reduced cell growth during early brain development can lead to smaller brain size. Our findings connect growth control and cellular energy balance, offering new insight into how brain development can be disrupted. (https://jmg.bmj.com/content/early/2026/03/19/jmg-2025-111242)