HMMR (hyaluronan-mediated motility receptor) is a multifunctional cell surface receptor that binds hyaluronic acid and regulates cellular processes critical to both normal physiology and cancer progression 1. The receptor mediates hyaluronan signaling through FAK/SRC-dependent pathways to activate downstream effectors including ERK and NF-κB signaling 2. HMMR coordinates spindle assembly, mitotic fidelity, and cell polarity while promoting cell migration and autophagy 13. In normal physiology, HMMR contributes to ovarian folliculogenesis and ovulation, with loss-of-function variants associated with premature ovarian insufficiency 4. In cancer biology, HMMR is consistently overexpressed across multiple malignancies including prostate, lung, gastric, and renal cell carcinomas, correlating with poor prognosis and therapeutic resistance 5678. HMMR drives metastasis through MAP4K4/JNK signaling in lung cancer and EMT/JAK1/STAT1 pathways in renal cancer 68. Functionally, HMMR sustains CD47-mediated immune evasion and suppresses phagocytic killing while maintaining cancer stem cells 21. In hepatocellular carcinoma, HMMR alleviates endoplasmic reticulum stress through autophagy promotion, facilitating HBV-driven transformation 3. These multifaceted roles position HMMR as both a prognostic biomarker and emerging therapeutic target.