Herein, we report that a severe HLD8-associated nonsense mutation of Arg550-to-Ter (R550X) localizes POLR3B proteins as aggregates, which is similar to other HLD-associated mutated proteins [13,14,15,16,17,18] in FBD-102b cell lysosomes, and it is used as an oligodendroglial precursor cell model. Here, POLR3B is linked to hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism.