Its pivotal role is strikingly illustrated by the fact that loss-of-function mutations lead to severe immunodeficiency, whereas gain-of-function mutations promote oncogenesis: For example, rare dysfunctional alleles of MYD88 compromise formation of the MyD88-mediated post-receptor complex (2), the so-called Myddosome (3, 4). The gene discussed is MYD88; the disease is Immunodeficiency.