Scara5, known as scavenger receptor class A member 5, has been implicated in multiple biological processes and diseases. It may play roles in regulating the clearance of VWF-FVIII as sinusoidal endothelial cell receptors variants in Scara5 are associated with plasma levels of VWF and/or FVIII in normal individuals [3]. It is also involved in various cancers, with implications for tumorigenesis and progression [1,2,4,5,6,7,8,9,10].

In cancer-related studies, in gastric cancer, Scara5 expression is downregulated, associated with promoter methylation. Overexpression of Scara5 suppresses the growth, migration, and invasion of gastric cancer cell lines in vitro and inhibits tumor growth and metastasis in a xenograft model by inhibiting epithelial-mesenchymal transition (EMT) and inactivating MMP-2 and MMP-9 [1].

In prostate cancer, high Scara5 expression is associated with advanced tumor stage, positive nodal status, and high Gleason-score, suggesting it might be a potential biomarker [2].

In colorectal cancer, Scara5 in bone marrow stromal cell-derived exosomes inhibits cancer progression by inactivating the PI3K/Akt pathway [4].

In bladder cancer, Scara5 expression is downregulated, and overexpression reduces cell viability, colony formation, invasion, and migration. It is a downstream factor of the PCAT29/miR-141 axis [5].

In oral squamous cell carcinoma, Scara5 overexpression inhibits cell proliferation, induces apoptosis, and represses EMT by inactivating the STAT3 and PI3K/AKT signaling pathways [6].

In esophageal squamous cell carcinoma, Scara5 is decreased, and overexpression suppresses cell cycle, metastasis, and invasion by inducing ferroptosis through combining with ferritin light chain [7].

In nasopharyngeal carcinoma, Scara5 is downregulated by promoter methylation, and its overexpression inhibits cell migration, invasion, and proliferation, and enhances sensitivity to chemotherapy [8].

In melanoma, decreased Scara5 expression is associated with TNM stage and recurrence, and high expression is related to better overall survival. It may be a prognostic biomarker and is related to immune infiltration levels [9].

In colorectal cancer, Scara5 mRNA levels are downregulated in cancer tissues, and low expression is associated with poor prognosis. Deep deletion is the common genetic alteration, and it may be a human cancer suppressor gene [10].

In conclusion, Scara5 is involved in multiple biological processes, especially in cancer development and progression. Its down-regulation in many cancers and the effects of its overexpression in inhibiting tumor-related phenotypes in various in vitro and in vivo models suggest its potential as a tumor suppressor and a valuable biomarker or therapeutic target in cancer. The studies on Scara5 contribute to a better understanding of cancer biology and may provide new strategies for cancer treatment.