Grem1, also known as Gremlin 1, is a BMP-antagonist. It belongs to a family of secreted cysteine-knot proteins that sequester and inhibit bone morphogenetic proteins (BMPs), preventing BMP-mediated activation of BMP type I and II receptors. Grem1 is involved in multiple biological processes such as embryonic development, organogenesis, and tissue differentiation [4,5].

In osteoarthritis (OA), Grem1-lineage chondrogenic progenitor cells are crucial. Ablation of Grem1-expressing cells in mice causes OA, suggesting that the loss of these progenitor cells, which are depleted by injury-induced OA and aging, contributes to the disease [1]. In pancreatic cancer, Grem1 inactivation in established PDAC in mice leads to a conversion of epithelial into mesenchymal PDAC cells, indicating its role in maintaining cellular heterogeneity [2]. In intervertebral disc degeneration (IVDD), the expression of Grem1 is positively correlated with the severity of IVDD, and Grem1 siRNA can inhibit apoptosis and extracellular matrix alterations in nucleus pulposus cells by mediating the TGF-β/Smad signaling pathway [3].

In conclusion, Grem1 is essential in maintaining normal tissue homeostasis. Mouse models with Grem1 ablation have revealed its significance in diseases like OA, pancreatic cancer, and IVDD. Understanding Grem1's functions provides potential therapeutic targets for these diseases.