Tinagl1, short for Tubulointerstitial nephritis antigen-like 1, is a matricellular protein involved in various biological processes. It plays roles in cell adhesion, and modulates cell proliferation, migration, and differentiation. It is associated with multiple signaling pathways such as integrin/FAK, EGFR, TGF-β, and ERK signaling pathways, which are crucial for normal physiological functions and are also involved in disease development [1,2,6,9].

In triple-negative breast cancer (TNBC), ectopic expression and therapeutic delivery of Tinagl1 suppress TNBC progression and metastasis by directly binding to integrin α5β1, αvβ1, and EGFR, and inhibiting FAK and EGFR signaling pathways [1]. In Crohn's Disease, mesenteric adipose-derived exosomal TINAGL1 enhances intestinal fibrosis via SMAD4 [2]. In breast cancer, low TINAGL1 expression is associated with poor prognosis [3]. In diabetes, down-regulated TINAGL1 in fibroblasts impairs wound healing, while exogenous TINAGL1 promotes wound healing in diabetic mice [4]. In TNBC, Tinagl1 gene therapy slows tumor growth, remodels the tumor microenvironment, and reduces the expression of Hif1a [5]. In hepatocellular carcinoma, TINAGL1 promotes carcinogenesis and metastasis via the TGF-β/Smad3/VEGF axis [6]. In esophageal cancer, YTHDF1 facilitates cancer progression by augmenting m6A-dependent TINAGL1 translation [7]. In Helicobacter pylori infection, TINAGL1 promotes gastric bacterial colonization and gastritis [8]. In muscle development, Tinagl1-deficient mice exhibit reduced body mass, abnormal muscle morphology, and decreased capillary density, suggesting Tinagl1 is required for normal muscle and capillary development through ERK signaling activation [9]. In tamoxifen-resistant breast cancer cells, Tinagl1 restores tamoxifen sensitivity and blocks fibronectin-induced EMT by blocking EGFR and β1-integrin/FAK signaling pathways [10].

In conclusion, Tinagl1 is involved in a wide range of biological functions, from normal muscle and capillary development to disease-related processes such as cancer progression, fibrosis, and wound healing. Gene-knockout and other loss-of-function experiments, especially in mouse models, have been instrumental in revealing its role in these specific biological processes and disease conditions, providing potential targets for therapeutic intervention in multiple disease areas.