POLR3K encodes a core component of RNA polymerase III (Pol III), which synthesizes small non-coding RNAs including tRNAs, 5S ribosomal RNA, and U6 small nuclear RNA 1. As part of the 17-subunit Pol III complex, POLR3K contributes to transcription fidelity by anchoring into the active site to monitor transcription and mediate proofreading of nascent RNA transcripts 2. The protein plays essential roles in RNA maturation and translation processes. Biallelic pathogenic variants in POLR3K cause POLR3-related hypomyelinating leukodystrophy (POLR3-HLD), also known as 4H leukodystrophy, characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism 31. Disease-causing mutations often impair normal assembly or biogenesis of the Pol III complex, causing retention of unassembled subunits in the cytoplasm 2. Patients with POLR3K variants present with neurological dysfunction including intellectual disability, behavioral disturbances, motor dysfunction, and distinctive craniofacial features 34. Only a few cases of POLR3K-associated disease have been reported worldwide, making it an extremely rare cause of leukodystrophy 3. The molecular mechanisms linking POLR3K mutations to tissue-specific hypomyelination remain incompletely understood 2.