Hapln1, short for hyaluronan and proteoglycan link protein 1, is a protein that maintains the aggregation and binding activity of extracellular matrix (ECM) molecules like hyaluronic acid and proteoglycan, stabilizing the ECM's macromolecular structure [4]. It is involved in multiple biological processes. For example, it can interact with versican to trap GDF11, activating the TGF-β/SMAD2/3 signaling pathway to promote the dedifferentiation and proliferation of iPSC-derived cardiomyocytes [3].

In disease-related studies, in pancreatic cancer, HAPLN1 in the extracellular matrix enhances tumor cell plasticity and metastasis, and is enriched in the basal subtype with worse patient survival [1]. In gastric cancer, cancer-associated fibroblasts-derived HAPLN1 promotes tumor invasion through ECM remodeling, and higher levels are associated with shorter overall survival [2]. In multiple myeloma, HAPLN1 confers drug resistance, and a matrikine derived from it promotes bone marrow homing of myeloma cells, correlating with poor progression-free survival [5,6]. In melanoma, age-dependent loss of HAPLN1 erodes vascular integrity via indirect upregulation of endothelial ICAM1 [7].

In conclusion, Hapln1 plays crucial roles in maintaining ECM structure and is involved in cell proliferation, differentiation, and immunomodulation. Through gene-knockout or conditional-knockout mouse models and other in vivo studies, its roles in various diseases such as pancreatic, gastric, and multiple myeloma cancers, as well as melanoma, have been revealed. Understanding Hapln1 provides insights into disease mechanisms and potential therapeutic targets.