DONSON (DNA replication fork stabilization factor) is a replisome component essential for DNA replication initiation and fork stability in vertebrates. DONSON scaffolds a pre-loading complex containing GINS, TOPBP1, and DNA polymerase ε, which it delivers to MCM2-7 complexes to facilitate CMG helicase assembly—the central event in origin activation 1. During replication initiation, DONSON interacts with TopBP1 in a CDK-dependent manner to promote Cdc45 and GINS chr21 association and helicase activation 2. Following initiation, DONSON remains part of the replisome during elongation and protects stalled or damaged replication forks, maintaining genome stability and enabling efficient intra-S-phase and G2/M checkpoint activation 3. Biallelic DONSON mutations cause microcephaly-micromelia syndrome and Meier-Gorlin syndrome, disorders characterized by primordial dwarfism and reduced brain size. Mechanistically, DONSON deficiency impairs CMG assembly, compromising DNA replication 1. In the developing nervous system, DONSON is critical for progenitors of cortical glutamatergic and GABAergic neurons; early telencephalic deletion causes extensive apoptosis and prevents neocortex formation, while subpallial deletion ablates 75% of cortical GABAergic neurons 3. These findings explain why the neocortex is severely affected in DONSON-mutant patients and establish DONSON dysfunction in genome instability pathways underlying neurological disease.