TLN1 encodes talin-1, a high molecular weight cytoskeletal protein that serves as a critical scaffold at focal adhesions, connecting integrins to the actin cytoskeleton 1. Talin-1 functions as a key regulator of cell adhesion and migration by mediating integrin-β1 binding and activating the FAK-AKT signaling pathway 1. The protein undergoes complex regulatory mechanisms, including ubiquitin-mediated degradation controlled by TRIM21 and stabilization through deubiquitination by USP25 23. In platelets, USP25-mediated talin-1 stabilization contributes to age-related platelet hyperreactivity and thrombosis risk 3. TLN1 expression is transcriptionally regulated by the cooperative interaction between FLI1 and GATA1 transcription factors, with defective cooperation leading to talin-1 deficiency and platelet dysfunction 4. Clinically, TLN1 dysregulation is implicated in multiple pathological conditions. Loss-of-function variants in focal adhesion scaffold genes including TLN1 contribute to thoracic aortic aneurysm pathogenesis by disrupting vascular smooth muscle cell contractility 5. Conversely, TLN1 overexpression promotes triple-negative breast cancer metastasis through enhanced focal adhesion dynamics and epithelial-mesenchymal transition 1. Additionally, TLN1 has been identified as a potential therapeutic target in migraine through genome-wide Mendelian randomization studies 6.