CPAP promotes timely cilium disassembly to maintain neural progenitor pool.

A mutation in the centrosomal‐P4.1‐associated protein (CPAP) causes Seckel syndromewith microcephaly, which is suggested to arise from a decline in neural progenitor cells (NPCs) during development. However, mechanisms of NPCs maintenance remain unclear. Here, we report an unexpected role for the ciliumin NPCs maintenance and identify CPAP as a negative regulator of ciliary length independent of its role in centrosomebiogenesis. At the onset of cilium disassembly, CPAP provides a scaffold for the cilium disassemblycomplex (CDC), which includes Nde1, Aurora A, and OFD1, recruited to the ciliary base for timely cilium disassembly. In contrast, mutated CPAP fails to localize at the ciliary base associated with inefficient CDC recruitment, long cilia, retarded cilium disassembly, and delayed cell cycle re‐entry leading to premature differentiation of patient iPS‐derived NPCs. Aberrant CDC function also promotes premature differentiation of NPCs in Seckel iPS‐derived organoids. Thus, our results suggest a role for cilia in microcephalyand its involvement during neurogenesis and brain sizecontrol.