POLR3-HLD, also termed 4H (Hypomyelination, Hypodontia, and Hypogonadotropic Hypogonadism) leukodystrophy, is caused by biallelic pathogenic variants in genes encoding subunits of the ubiquitous RNA polymerase III (Pol III) enzymatic complex (e.g., POLR3A, POLR3B, POLR1C, POLR3K, and POLR3D) [4,14,15,16,22] (Figure 2). The gene discussed is POLR3B; the disease is leukodystrophy.