SMAD3 is a protein intracellular signal transducer that is part of the TGF-β (transforming growth factor-beta) superfamily signaling pathway. When SMAD3 is phosphorylated at serine residues 423 and 425 (referred to as SMAD3 (phospho S423+S425)), it indicates activation of the TGF-β signaling cascade within a cell. This phosphorylation event typically occurs after SMAD3 binds to the activated TGF-β receptor, leading to its phosphorylation and subsequent interaction with SMAD4. Together, they accumulate in the nucleus where they regulate gene expression associated with various cellular processes, including cell growth, differentiation, and immune responses. In the context of disease research, understanding SMAD3 phosphorylation is particularly relevant in conditions such as cancer, where dysregulation of TGF-β signaling can contribute to tumor progression and metastasis. SMAD3 is also implicated in fibrotic diseases, cardiovascular diseases, and immune responses, making it a potential therapeutic target for these conditions.