Kidney injury molecule 1 (KIM-1), encoded by HAVCR1, was initially identified as one of the most highly induced proteins in injured proximal tubule epithelial cells and subsequently established as a sensitive tissue, urinary, and circulating biomarker of kidney injury. Yet KIM-1 is not just a marker of epithelial damage. It is a phosphatidylserine receptor that enables injured proximal tubule cells to recognize and internalize apoptotic cells and luminal cargo. This process engages intracellular trafficking, autophagy-related processing, and immune regulatory pathways, with consequences that are highly context-dependent. Transient KIM-1 expression can promote debris clearance and limit inflammation after acute injury, whereas sustained expression and uptake of protein- and lipid-rich cargo can contribute to cellular stress, maladaptive repair, inflammation, and fibrosis. Beyond kidney injury, KIM-1 is expressed and shed by renal cell carcinomas, in which circulating levels carry diagnostic, prognostic, and potentially treatment-stratifying information. KIM-1 is also emerging as both a molecular address for targeted therapeutic delivery and a candidate for functional inhibition or degradation. This review traces how KIM-1 evolved from an injury-induced transcript to a biomarker, signaling receptor, disease mediator, and therapeutic target. We propose a framework in which expression duration, cargo identity, receptor processing, intracellular trafficking, and disease context determine whether KIM-1 supports repair or promotes pathology, highlighting unresolved questions essential for translating its complex biology into more precise diagnostic and therapeutic strategies.
