Beyond their critical role in normal cellular functions, SAMD9 and SAMD9L are also involved in several severe genetic disorders, including MIRAGE syndrome, ataxia-pancytopenia (ATXPC) syndrome, myeloid leukemia syndrome with monosomy 7 (MLSM7), refractory cytopenia of childhood (RCC), or SAMD9L-associated autoinflammatory disease (SAAD) [13,18,20–24]. Here, SAMD9 is linked to hereditary disease.