PCH2D is caused by mutations in the SEPSECS gene that encodes SepSecS, an enzyme in the last step of the selenocysteine production pathway that catalyzes the conversion of O-phosphoseryl-tRNA(Sec) to selenocysteinyl-tRNA (Fig. 1c) [31, 32]. The gene discussed is SEPSECS; the disease is pontocerebellar hypoplasia type 2D.