PRDX6 enhances selenium utilization to limit iron toxicity and ferroptosis. Ferroptosis is a form of regulated cell death caused by iron-dependent accumulation of lipid hydroperoxides. Selenoprotein glutathione peroxidase 4 (GPX4) suppresses ferroptosis by detoxifying lipid hydroperoxides. PRDX6, a novel selenoprotein synthesis factor, increases intracellular selenium utilization by transferring selenium between proteins in the selenocysteyl-tRNA synthesis machinery, leading to efficient selenocysteyl-tRNA synthesis. Loss of PRDX6 reduces selenoprotein expression and induces ferroptosis by decreasing GPX4 levels. PRDX6 functions as a selenide carrier, transferring selenide to SEPHS2 to facilitate efficient selenium utilization. PRDX6 is involved in selenoprotein synthesis and selenium metabolism, and its loss reduces selenoprotein expression and increases ferroptosis sensitivity. PRDX6 is also involved in efficient utilization of selenium for Sec-tRNA synthesis. PRDX6 is a selenide carrier protein that facilitates the efficient utilization of selenium by SEPHS2. PRDX6 is involved in the metabolism of selenium and its delivery to SEPHS2. PRDX6 is a potential target for cancer therapy as its loss is associated with poor prognosis in cancer patients. PRDX6 is a selenide carrier protein that enables efficient selenium utilization, which is essential for selenoprotein synthesis and the suppression of ferroptosis. The identification of PRDX6 as a selenium carrier protein opens new avenues for research into intracellular selenium dynamics. PRDX6 is a selenide carrier protein that facilitates the efficient utilization of selenium by SEPHS2, which is essential for selenoprotein synthesis and the suppression of ferroptosis. PRDX6 is a potential target for cancer therapy as its loss is associated with poor prognosis in cancer patients.PRDX6 enhances selenium utilization to limit iron toxicity and ferroptosis. Ferroptosis is a form of regulated cell death caused by iron-dependent accumulation of lipid hydroperoxides. Selenoprotein glutathione peroxidase 4 (GPX4) suppresses ferroptosis by detoxifying lipid hydroperoxides. PRDX6, a novel selenoprotein synthesis factor, increases intracellular selenium utilization by transferring selenium between proteins in the selenocysteyl-tRNA synthesis machinery, leading to efficient selenocysteyl-tRNA synthesis. Loss of PRDX6 reduces selenoprotein expression and induces ferroptosis by decreasing GPX4 levels. PRDX6 functions as a selenide carrier, transferring selenide to SEPHS2 to facilitate efficient selenium utilization. PRDX6 is involved in selenoprotein synthesis and selenium metabolism, and its loss reduces selenoprotein expression and increases ferroptosis sensitivity. PRDX6 is also involved in efficient utilization of selenium for Sec-tRNA synthesis. PRDX6 is a selenide carrier protein that facilitates the efficient utilization of selenium by SEPHS2. PRDX6 is involved in the metabolism of selenium and its delivery to SEPHS2. PRDX6 is a potential target for cancer therapy as its loss is associated with poor prognosis in cancer patients. PRDX6 is a selenide carrier protein that enables efficient selenium utilization, which is essential for selenoprotein synthesis and the suppression of ferroptosis. The identification of PRDX6 as a selenium carrier protein opens new avenues for research into intracellular selenium dynamics. PRDX6 is a selenide carrier protein that facilitates the efficient utilization of selenium by SEPHS2, which is essential for selenoprotein synthesis and the suppression of ferroptosis. PRDX6 is a potential target for cancer therapy as its loss is associated with poor prognosis in cancer patients.