Now known to be one of the most common hypomyelinating leukodystrophies, POLR3-related leukodystrophy arises from biallelic pathogenic variants in genes that encode subunits of RNA polymerase III (Pol III), namely POLR3A, POLR3B, POLR1C, and POLR3K (Bernard et al., 2011; Tétreault et al., 2011; Thiffault et al., 2015; Dorboz et al., 2018; Schmidt et al., 2020). The gene discussed is POLR3A; the disease is leukodystrophy.