POLR3GL encodes a peripheral subunit of RNA polymerase III (Pol III), a multi-subunit complex responsible for transcribing small housekeeping RNAs including 5S ribosomal RNA, transfer RNAs, and U6 small nuclear RNA 1. POLR3GL is one of two paralogous subunits (RPC7β) that can incorporate into Pol III complexes; the other variant contains POLR3G (RPC7α). Unlike POLR3G, POLR3GL is ubiquitously expressed across tissues 2. Both POLR3G- and POLR3GL-containing Pol III forms occupy identical target genes with similar proportions, suggesting functional equivalence regarding target gene specificity 3. However, they differ in regulation: only the POLR3G promoter binds MYC transcription factor 3. POLR3GL and POLR3G can partially compensate for each other in vivo; POLR3GL knockout mice survive embryogenesis but die postnatally with growth defects and neuronal abnormalities 4. Biallelic POLR3GL mutations cause endosteal hyperostosis, oligodontia, short stature, and facial dysmorphisms, representing a rare POLR3-related developmental disorder 5. POLR3GL mutations should be included in genetic testing for suspected POLR3-related disorders 5.