The field of inborn errors of immunity (IEI) is advancing at a remarkable pace, driven by next-generation sequencing, functional genomics, and an ever-expanding understanding of the molecular pathways that underpin human immune function. In this Special Issue, we bring together contributions that reflect the breadth and dynamism of this discipline. A central theme of this Issue is the growing complexity of genotype–phenotype relationships. Phenocopies produced by autoantibodies against cytokines — challenge our diagnostic frameworks and demand a broader conceptual approach. Equally, incomplete penetrance reminds us that a pathogenic variant is rarely the whole story, and that modifier genes, environmental triggers, and stochastic events all shape clinical outcome. Somatic mosaicism adds yet another layer, revealing how post-zygotic mutations can produce attenuated or atypical disease presentations that may otherwise elude diagnosis. This Issue also explores the increasingly recognised overlap between IEI and inborn errors of metabolism, underscoring that immune dysfunction does not exist in isolation from broader cellular homeostasis. Similarly, the intersection of IEI with cytopenias and lymphoproliferation represents a clinically important frontier, where haematological and immunological expertise must converge. Finally, we wish to highlight the profound impact that studying rare monogenic IEI has on our understanding of common disease: the identification of monogenic and autoimmune causes of variable susceptibility to infection has fundamentally reshaped our view of infectious disease. In addition, novel insights into severe allergy have had implications far beyond the rare disease community. Similarly, the recognition of monogenic IEI as a cause of for instance lupus challenge our view on common immune conditions, rarely thought of as genetic. Here we welcome all manuscripts focusing on one or more of these aspects of our interesting field.