Tinagl1, short for Tubulointerstitial nephritis antigen-like 1, is a matricellular protein involved in multiple biological processes. It is associated with cell adhesion and can modulate cell proliferation, migration, and differentiation. It interacts with pathways such as integrin/FAK, EGFR, TGF-β, and ERK, playing a significant role in various physiological and pathological conditions [1,2,6,9].

In breast cancer, Tinagl1 has emerged as a crucial factor. Ectopic expression and therapeutic delivery of Tinagl1 protein suppress triple-negative breast cancer (TNBC) progression and metastasis by simultaneously inhibiting integrin/FAK and EGFR signaling [1]. Low Tinagl1 expression is a marker for poor prognosis in breast cancer patients, especially in hormone-receptor-positive/human epidermal-growth-factor-receptor-2-negative and pre-menopausal patients [3]. In TNBC, Tinagl1 gene therapy can slow tumor growth, remodel the tumor microenvironment by increasing vasculature without increasing metastasis risk, and reduce Hif1a expression [5]. In tamoxifen-resistant breast cancer cells, Tinagl1 can restore tamoxifen sensitivity and block fibronectin-induced EMT by blocking EGFR and β1-integrin/FAK signaling [10].

In Crohn's disease, mesenteric adipose-derived exosomal TINAGL1 enhances intestinal fibrosis via SMAD4 [2].

In diabetes, decreased TINAGL1 expression in fibroblasts impairs wound healing, while exogenous TINAGL1 promotes wound healing in diabetic mice [4].

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 conclusion, Tinagl1 plays diverse and essential roles in multiple biological processes and disease conditions. Research using gene knockout or knockdown models in various systems, such as mice, has significantly contributed to understanding its functions in diseases like cancer, inflammatory bowel disease, diabetes-related wound healing, and muscle development. These findings highlight Tinagl1 as a potential biomarker and therapeutic target in multiple disease areas.