RORC is a nuclear receptor transcription factor essential for lymphoid tissue development and adaptive immunity. It serves as a master regulator of group 3 innate lymphoid cells (ILC3s) and T helper 17 (Th17) cell differentiation 1. Downstream of IL-6 and TGF-β signaling, RORC drives Th17 lineage specification by binding to conserved enhancer elements in the IL17-IL17F locus and recruiting coactivators, while simultaneously antagonizing the Th1 program. RORC-expressing antigen-presenting cells, including ILC3s and dendritic cell subsets, promote differentiation of peripherally-induced regulatory T cells that maintain tolerance to commensal microbiota and dietary antigens, thereby preventing excessive inflammatory responses 2. Rorc dysregulation contributes to multiple inflammatory and autoimmune diseases. In inflammatory bowel disease, enrichment of the bacterium Eggerthella lenta drives Th17-dependent colitis through mechanisms that lift inhibition of RORC 3. In rheumatoid arthritis, macrophage migration inhibitory factor promotes Th17 differentiation by enhancing ATF6-mediated RORC transcription 4. Recent evidence indicates that RORC-expressing cells negatively regulate tertiary lymphoid structure formation in liver cancer, and their absence shifts these structures from pro-tumorigenic to anti-tumorigenic phenotypes 5. Rare nonsense variants in RORC have been associated with lymphedema in patients negative for known causative genes 6. Vitamin A supplementation reduces RORC expression and IL-17 production in atherosclerotic patients, suggesting potential therapeutic modulation 7.