SLAMF1 at the crossroads of immunity and disease: Biology, pathology, and therapeutic opportunities.

Signaling lymphocytic activation molecule family member 1 (SLAMF1/CD150) is a multifunctional receptor that regulates both innate and adaptive immunity. Through homophilic interactions and SAP-dependent signaling, SLAMF1 supports invariant natural killer T (iNKT) cell selection, γδ T cell polarization, and natural killer (NK) cell education. It also modulates germinal center dynamics and humoral responses, often in cooperation with other SLAM receptors. Beyond lymphoid compartments, SLAMF1 functions as a microbial sensor in macrophages, promotes phagosome maturation, reactive oxygen species production, and regulates Toll-like receptor 4 (TLR4)-mediated pathways, thereby linking innate recognition to antimicrobial defense. Dysregulation of SLAMF1 has been implicated in diverse pathological conditions. In chronic lymphocytic leukemia, its loss associates with genomic instability, poor outcomes, and therapy resistance, while in trophoblastic tumors and renal cell carcinoma, elevated expression sustains tumor survival and progression. In autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis, SLAMF1 drives pathogenic T-B collaboration and chronic inflammation. Infectious disease studies further highlight its role as both a pathogen sensor and viral entry receptor. Recent therapeutic advances, including SLAMF1-derived peptides, offer innovative strategies for modulating inflammation, protecting against cardiac injury, and selectively inducing tumor cell apoptosis. These findings establish SLAMF1 as a biomarker and promising therapeutic target, warranting further translational investigation.