What We Know and What We Don't Know About the Function of γδ T Cells

γδ T cells, long regarded as unconventional relatives of αβ T cells, have emerged as pivotal players in immunity, with unique biology and therapeutic promise. Recent advances in single-cell multiomics, refined mouse models, and human cohort studies have deepened insights into their TCR–ligand interactions, developmental pathways, and context-dependent functions. This mini-review synthesizes current understanding from structural studies of γδ TCR recognition and developmental regulation—including inborn errors of immunity—to adaptive-like clonal expansions shaped by infection, aging, and environmental cues. It also highlights their dual roles in cancer, where subsets can exert potent cytotoxicity or promote tumor progression, and discusses strategies to optimize their antitumor potential through checkpoint blockade, metabolic modulation, and engineered receptors. Beyond immunity to malignancy, γδ T cells contribute to tissue homeostasis, repair, and regulation of inflammatory processes in diverse organs, influencing outcomes in neuroinflammation, autoimmunity, and fibrotic diseases. Together, these perspectives form the foundation of a special issue in the European Journal of Immunology (https://onlinelibrary.wiley.com/doi/toc/10.1002/(ISSN)1521-4141.T-cells) dedicated to advancing the understanding of γδ T cell biology and clinical potential.