In higher vertebrates, multicilia are important for luminal flow and for the removal of thick mucus, and they form in specialized terminally differentiated epithelial cells. As each cilium requires a centriole, these cells must undergo massive centriole amplification to generate hundreds of centrioles. Although some are generated through a mother centriole-dependent (MCD) pathway, the majority are formed through a de novo pathway, which is mediated by a structure known as a deuterosome. Zhao et al. find that the deuterosome-dependent pathway is governed by DEUP1 (deuterosome protein 1), a paralogue of CEP63 (centrosomal protein 63). In the same way that CEP63 binds to CEP152 and then recruits PLK4 (polo-like kinase 4) to activate MCD centriole biogenesis, CEP63 binds to CEP152 and then recruits PLK4 for de novo formation of centrioles in multiciliated cells.