14-3-3 sigma (also known as SFN or stratifin) is a member of the highly conserved 14-3-3 protein family, functioning as a negative regulator of the cell cycle. It is primarily induced by p53 and plays a crucial role in initiating and maintaining cell cycle checkpoints after DNA damage, particularly arresting the cell cycle at the G2/M phase. This protein acts as a tumor suppressor in various cancers by regulating the stability of tumor suppressor genes and inhibiting cell proliferation. Additionally, 14-3-3 sigma interacts with multiple proteins to modulate signaling pathways, such as Akt/mTOR, and can influence processes like protein synthesis and cell growth. Its dysregulation is associated with chemoresistance and poor prognosis in several malignancies, highlighting its potential as a therapeutic target.