TP53INP1 (tumor protein p53 inducible nuclear protein 1) is a multifunctional stress-response protein acting as a dual regulator of transcription and autophagy with tumor suppressive properties. Primary function: TP53INP1 operates through two major mechanisms. In the nucleus, it directly interacts with p53 and p73 transcription factors to enhance their apoptotic and cell-cycle regulatory capacity 1, particularly in response to double-strand DNA breaks [UniProt]. Cytoplasmic TP53INP1 acts as an autophagic receptor, binding ATG8 family proteins (especially LC3C) and promoting autophagosome assembly 23. Mechanism: TP53INP1 possesses intrinsic antioxidant activity, regulating mitochondrial reactive oxygen species production both p53-dependently and independently 1. It also localizes to lysosomes during autophagy to maintain lysosomal ROS homeostasis and enzymatic function 2. Disease relevance: TP53INP1 downregulation is associated with multiple cancers; miR-504 and miR-200a suppress TP53INP1 expression to promote osteosarcoma and breast cancer growth/metastasis respectively 45. Additionally, TP53INP1 upregulation confers paclitaxel chemosensitivity 6, and genetic variants affecting TP53INP1 expression are implicated in type 2 diabetes susceptibility 7. TP53INP1 is essential for radiation-induced autophagy and survival 8, functioning as a critical metabolic homeostasis regulator 1.