IFNG (interferon gamma) is a type II interferon produced by T cells and NK cells that orchestrates antimicrobial, antiviral, and antitumor immunity 1. The protein signals primarily through the JAK-STAT pathway: upon binding its receptor IFNGR1, JAK1/JAK2 kinases activate STAT1, which translocates to the nucleus and initiates transcription of interferon-stimulated genes (ISGs) including transcription factors like IRF1 1. IFNG enhances antigen presentation by inducing immunoproteasome subunit replacement and PA28 expression, increasing peptide quality and quantity for MHC-I loading 234. It upregulates MHC-II complexes through cathepsin induction 5. IFNG polarizes macrophages toward the pro-inflammatory M1 phenotype 6. Clinically, IFNG signaling has dual roles in cancer immunity: while promoting exhaustion through PDL1 upregulation in tumor cells, it simultaneously activates innate immune effector cells in favorable tumor contexts 7. In rectal cancer, total neoadjuvant therapy increases IFNG-expressing CD8+ effector memory T cells, correlating with improved response rates 8. IFNG polymorphisms influence disease susceptibility; the +874T allele associates with leprosy resistance, potentially through enhanced interferon production 9. Dysregulation associates with immunodeficiency and age-related conditions including hearing loss 10.