GREM1 is a BMP antagonist that plays critical roles in both developmental and pathological contexts. Functionally, GREM1 inhibits bone morphogenetic protein (BMP) signaling by binding BMPs and blocking their receptor-mediated effects 1, thereby suppressing osteoblast differentiation and bone remodeling 2. In pancreatic ductal adenocarcinoma (PDAC), GREM1 secreted by mesenchymal cells maintains epithelial cell fate by continuously suppressing BMP signaling, preventing epithelial-to-mesenchymal transition through inhibition of Snail transcription factors 2. This paracrine signaling is essential for maintaining cellular heterogeneity and forms part of a reciprocal regulatory loop with SPP1 1. In colorectal cancer (CRC), elevated GREM1 levels are causally associated with increased CRC risk and poor survival, with high GREM1 expression in cancer-associated fibroblasts promoting tumorigenesis 34. GREM1 is implicated in hereditary polyposis syndrome, linking it to genetic predisposition to colorectal cancer 5. Beyond cancer, GREM1 overexpression accelerates intervertebral disc degeneration by promoting nucleus pulposus cell apoptosis through inhibition of TGF-β/Smad signaling 6, and elevated GREM1 promotes hepatic cell senescence in NAFLD/NASH by antagonizing BMP4's protective effects 7. Clinically, GREM1 represents a therapeutic target in multiple diseases through BMP pathway modulation.