Considering the clinical relevance of anti-CD38-based therapies in MM, we envisage that a combined strategy that aims to upregulate CD38 surface availability to exploit the anti-tumor activity of NAD+-depleting agents could be particularly important to eliminate MM cells expressing very low CD38 levels, including low proliferative or dormant MM-initiating cells or drug-resistant clones with minimal residual disease eradication. The gene discussed is CD38; the disease is Miyoshi myopathy.