However, an emerging concern for both protein and gene replacement lies in the sensitivity of cells to CDKL5 dosage, particularly when reintroducing the protein into wild-type cells, a scenario that is highly relevant to female CDD patients with mosaic loss of CDKL5, or in tissues with low or absent CDKL5 expression. The gene discussed is CDKL5; the disease is craniodiaphyseal dysplasia.