Biallelic disease-causing variants in the PSAP gene, which encodes the protein activator saposin B (SapB), cause SapB-dependent MLD (OMIM #249900).4 Biallelic disease-causing variants in the SUMF1 gene, a gene essential for posttranslational modification of sulfatase enzymes, results in multiple sulfatase deficiency (MSD, OMIM #272200) (Figure 1).4,5 In MSD, sulfatides as well as other sulfated molecules, including steroid sulfates and glycosaminoglycans, accumulate, creating a biochemical profile that, for sulfatides, resembles MLD. Here, PSAP is linked to metachromatic leukodystrophy.