SPOCK2, also known as SPARC/osteonectin, cwcv and kazal-like domains proteoglycan 2, is a 424-amino acid protein that binds to glycosaminoglycans to form proteoglycans. It is involved in multiple biological processes. In the extracellular matrix, it may play roles in cell-matrix interactions, and is associated with pathways like Wnt/β-catenin [1,3].

In ovarian cancer, SPOCK2 overexpression promotes malignant behavior, as SPOCK2 downregulation suppresses cell proliferation, migration, invasion, and promotes apoptosis, and it can regulate the Wnt/β-catenin signaling pathway [1].

In lung adenocarcinoma, EZH2 suppresses SPOCK2 expression, and SPOCK2 overexpression inhibits tumoral proliferation, migration, and invasion in vitro and retards tumor growth in vivo [2].

In pancreatic ductal adenocarcinoma, SPOCK2 expression is downregulated due to gene hypermethylation, and high SPOCK2 expression correlates with longer patient survival [4].

In sepsis-induced cardiomyopathy, SPOCK2 expression increases in septic cardiac endothelial cells and may play a protective role, as its deletion increases LPS-induced apoptosis and necrosis in human umbilical vein endothelial cells [5].

In endometrial cancer, low SPOCK2 expression is associated with metastasis and invasion, and upregulation of SPOCK2 inhibits cell proliferation, invasion, adhesion, and apoptosis by regulating MT1-MMP and MMP2 [6,7].

In endometriosis, downregulation of SPOCK2 promotes the proliferation, adhesion, and invasion of endometrial epithelial cells [8].

In summary, SPOCK2 plays diverse roles in different biological processes and diseases. Its functions in cancer often relate to regulating cell proliferation, migration, invasion, and apoptosis, and in sepsis-induced cardiomyopathy, it has a potential protective role in endothelial cells. These findings from various studies contribute to understanding the biological functions of SPOCK2 and its implications in disease development, providing potential directions for targeted therapies.