TLR7 is an endosomal pattern recognition receptor critical for innate and adaptive immunity 1. It recognizes viral uridine-containing single-stranded RNA and guanosine analogs 23, with ligand binding occurring in two distinct pockets that recognize guanosine and pyrimidine-rich RNA fragments 4. Upon agonist binding, TLR7 dimerizes and recruits the adaptor protein MyD88, triggering assembly of the Myddosome complex containing IRAK4, IRAK1, TRAF6, and TRAF3, ultimately activating NF-κB and IRF7 transcription factors 3. In plasmacytoid dendritic cells, RNase T2 and PLD3/PLD4 exonucleases process RNA to generate 2',3'-cGMP and pyrimidine-rich fragments that occupy TLR7 ligand-binding pockets 4. TLR7 escapes X-chromosome X in immune cells, contributing to the female predominance of autoimmune disease 5. Gain-of-function TLR7 variants and UNC93B1 mutations that enhance TLR7 trafficking cause systemic lupus erythematosus through aberrant B cell activation and survival 67. TLR7 also drives psoriasis pathogenesis via myeloid cell activation 8. Pseudouridine-modified RNA evades TLR7 detection through impaired enzymatic processing and direct ligand evasion, providing a safety mechanism exploited in mRNA therapeutics 9.