Unregulated gene expression can for some diseases be detrimental exemplified by the CD40LG gene, which must be expressed at controlled levels as evidenced by preclinical mouse studies where ex vivo gene therapy in a mouse model of X-linked hyper-IgM syndrome with CD40LG-encoding murine gamma-retroviral vectors in HSCs led to lymphoproliferative disorder assumingly as a consequence of unregulated expression of the CD40L transgene (Glessner et al., 2017). The gene discussed is CD40LG; the disease is X-linked hyper-IgM syndrome.