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). This evidence concerns the gene POLR3K and leukodystrophy.