Genetic mutations in several Pol III subunits result in a variety but overlapping set of disease states, including autoimmune conditions initiated by genetic alterations of POLR3A in cancer (Joseph et al., 2014), immunodeficiencies caused by mutation events in POLR3A, POLR3C, POLR3E, and POLR3F (Carter-Timofte et al., 2019), and hypomyelinating leukodystrophy and related neurodegenerative conditions caused by distinct mutations in POLR3A, POLR3B, POLR1C, and POLR3K (Lata et al., 2021; Moir et al., 2021). The gene discussed is POLR3A; the disease is leukodystrophy.