RORC (RAR related orphan receptor C) is a nuclear receptor transcription factor essential for immune system development and function. Structurally, RORC functions as a DNA-binding transcription factor that regulates target genes through interaction with ROREs (RORC response elements) in promoter regions 1. Primary developmental functions include orchestrating thymopoiesis and secondary lymphoid tissue organogenesis, including lymph nodes and Peyer's patches 1. RORC is critical for generating lymphoid tissue inducer (LTi) cells and innate lymphoid cell (ILC) differentiation, wherein Notch signaling upregulates RORC to enable ILC3 acquisition of Group 3 effector functions producing IL-17A and IL-22 2. RORC's most characterized function involves CD4+ T helper differentiation. Downstream of IL-6 and TGF-β signaling, RORC synergistically with RORA drives uncommitted CD4+ T cells toward Th17 lineage specification, antagonizing Th1 differentiation by regulating IL17 and IL17F expression at the CNS2 enhancer 1. Multiple bacterial species—including Eggerthella lenta and Alcaligenes faecalis—enhance RORC transcription to promote Th17 differentiation 34. Beyond Th17 differentiation, RORC mediates immune tolerance. RORC-expressing antigen-presenting cells, particularly ILC3s and specialized dendritic cells, promote pTreg differentiation to suppress inflammatory responses to commensal microbiota and dietary antigens 5. RORC also regulates tertiary lymphoid structure formation and immune homeostasis in liver cancer 6. Disease associations include immunodeficiency 42 and lymphedema, with rare RORC variants identified in lymphedema patients 7. RORC dysfunction correlates with type 2 diabetes pathophysiology, as RORB and RORC expression associates with insulin secretion capacity 8.