SECTM1 coordinates immune microenvironments and multi-systemic disease pathophysiology.

Secreted and Transmembrane Protein 1 (SECTM1) is a versatile immunomodulatory protein that exists in both membrane-bound and soluble forms. Initially identified for its interaction with the T-cell receptor CD7, it was primarily regarded as a co-stimulatory molecule restricted to lymphoid signaling. Recent evidence has significantly expanded this paradigm, revealing that SECTM1 serves as a pivotal bridge between innate and adaptive immune responses. Beyond its classic role, SECTM1 interacts with alternative receptors like the glucocorticoid-induced TNFR-related protein to regulate macrophage activity and neutrophilic inflammation. This review highlights a major shift in our understanding of SECTM1: it acts as a multi-systemic regulator that influences the tumor microenvironment, metabolic homeostasis, and tissue regeneration. We systematically delineate the molecular mechanisms by which SECTM1 governs immune cell migration and activation across diverse pathologies, including cancer, cardiovascular disorders, and neurodegenerative diseases. By positioning SECTM1 as a marker of "immune-hot" tumors and a potential early diagnostic biomarker for systemic conditions, this work underscores its emerging clinical potential as a target for precision immunotherapy and regenerative medicine.