POLR3H encodes RNA polymerase III (Pol III) subunit H, a peripheral component of the Pol III complex that catalyzes transcription of DNA into RNA 1. As part of Pol III, POLR3H participates in synthesizing small non-coding RNAs including 5S rRNA, tRNAs, snRNAs, and miRNAs. POLR3H forms a mobile stalk structure with CRCP/RPC9 that functions primarily in transcription initiation 1. Beyond its canonical transcriptional role, Pol III functions as a nuclear and cytosolic DNA sensor in innate immunity, detecting non-self dsDNA and triggering type I interferon responses through the RIG-I pathway 1. Clinically, POLR3H mutations cause primary ovarian insufficiency (POI), a form of female infertility characterized by premature ovarian failure before age 40 2. A pathogenic homozygous missense mutation (p.Asp50Gly) in POLR3H was identified in families with idiopathic POI 2. Mouse models carrying this mutation showed delayed pubertal development, decreased fertility, reduced ovarian Foxo3a expression, and diminished primary follicle numbers 2. POLR3H mutations represent a rare but important genetic cause of POI, supporting the need for genetic screening to improve counseling and patient management 3. POLR3H also appears implicated in neurological traits through brain-specific expression quantitative trait loci associations 4.