The immune system relies on a complex network of receptor-ligand interactions to distinguish self from non-self, maintain immune tolerance, and mount effective responses against infection, malignancy, and foreign tissue. These processes are shaped by extensive genetic diversity across immune-related genes involved in antigen presentation, immune recognition, and cellular signaling. Among the most extensively studied are the human leukocyte antigen (HLA) genes on chromosome 6 and the killer-cell immunoglobulin-like receptor (KIR) and leukocyte immunoglobulin-like receptor (LILR) gene families on chromosome 19, which play central roles in immune recognition and regulation. HLA molecules present peptide antigens to T cells, while KIR and LILR receptors regulate immune-cell activation and inhibition. Equally important are the T-cell receptor (TCR) loci (TRA, TRB, TRG, and TRD), which govern antigen recognition by T lymphocytes, and the immunoglobulin loci (IGH, IGK, and IGL), which encode the antibody repertoire of B cells. Variation within these loci, particularly the highly complex IGH region, contributes substantially to differences in immune responses among individuals and populations. Additional polymorphic gene families, including Fc receptors, cytokines and cytokine receptors, complement components, Toll-like receptors (TLRs), NOD-like receptors (NLRs), and C-type lectin receptors, further shape innate and adaptive immunity. Genetic variation across immune-related loci has been associated with susceptibility to or protection from autoimmune and inflammatory disorders, infectious diseases, cancer, reproductive disorders, and transplant outcomes. In transplantation medicine, HLA and KIR variation remain major determinants of donor-recipient compatibility and graft survival. Advances in high-throughput sequencing, long-read genomics, and immunogenomic analyses are now enabling increasingly comprehensive characterization of complex immune gene regions that were previously difficult to resolve. Beyond humans, orthologous and functionally analogous immune receptor systems have been characterized across a wide range of vertebrate species, including non-human primates, rodents, birds, and many others. Comparative genomic studies have revealed both conserved mechanisms of immune recognition and remarkable lineage-specific diversification, providing insights into host-pathogen co-evolution and the evolutionary forces shaping immune system diversity. These investigations have important implications for human health, veterinary medicine, wildlife biology, and the development of translational animal models. This Special Issue, organized by the Society for Immune Polymorphism, invites articles that advance our understanding of immune genetic diversity and immunogenomics, including but not limited to the following themes: - Genomic structure, allelic diversity, structural variation, copy-number variation, and haplotype organization of immune-related gene families, including HLA, KIR, LILR, TCR, immunoglobulin (IGH, IGK, and IGL), Fc receptor, cytokine, complement, and innate immune receptor loci, as well as non-classical MHC molecules, including MR1, CD1, HLA-E, and HLA-G, and their consequences to immune function, evolution, and disease risk. - Genetic determinants of susceptibility, resistance, progression, and clinical outcomes in infectious diseases, autoimmune disorders, inflammatory conditions, cancer, reproductive disorders, and transplantation - Functional consequences of immune genetic variation on immune-cell development, immune regulation, host-pathogen interactions, disease pathogenesis, and therapeutic response - Immunobiology and immunogenetics of unconventional T cell subsets, including Mucosal Associated Invariant T (MAIT) cells, Natural Killer T (NKT) cells, and γδ T cells, with emphasis on the genetic and functional diversity of their antigen-presenting molecules and ligand repertoires - Molecular mechanisms linking immune gene variation to disease, including receptor-ligand interactions, signaling pathways, immune tolerance, and immune evasion - Population genetics, evolutionary biology, and comparative genomics of immune gene systems, with emphasis on their implications for disease susceptibility and adaptation - Immunogenomic studies of infectious diseases, cancer immunology, autoimmunity, transplantation, and other immune-mediated disorders - Development and application of genomic, transcriptomic, epigenomic, and computational approaches for the characterization of complex immune gene regions and their contribution to disease risk - Translational applications of immune genetics and immunogenomics in diagnostics, prognostics, biomarker discovery, precision medicine, vaccine development, and immunotherapy - Comparative immunogenomics and immune receptor diversity in human and non-human species, particularly where these studies provide insights into immune function, disease mechanisms, or translational animal models. Contributions addressing any of these themes, including cross-disciplinary and translational perspectives, are warmly welcomed.