As recently reported in the case of SAMD4A knockdown in osteosarcoma epithelial cells (Fernandez-Alvarez et al., 2022), defects in the formation of SAMD4A-mediated proteinaceous MLOs sequestering mRNAs lead to failures in mRNA repression and a release of unnecessary mRNAs that triggers inopportune protein translation. The gene discussed is SAMD4A; the disease is osteosarcoma.