NUFIP1 (nuclear FMR1 interacting protein 1) is a multifunctional protein with primary roles in selective autophagy and cellular stress response. Its best-characterized function is as a mammalian ribophagy receptor that selectively targets ribosomes for autophagic degradation during nutrient starvation 1. Upon mTORC1 inhibition, NUFIP1 redistributes from the nucleus to autophagosomes where it binds LC3B and delivers ribosomes for lysosomal degradation, promoting cell survival under starvation conditions 1. Beyond ribophagy, NUFIP1 integrates amino acid sensing with DNA damage response (DDR) signaling by phosphorylation-dependent binding to RPA32, recruiting the ATR-ATRIP complex to trigger DDR activation 2. Loss of NUFIP1 impairs DDR function and induces necroptosis-related intestinal inflammation, with NUFIP1 protein levels significantly reduced in inflammatory bowel disease patients 2. NUFIP1 also functions as a selective autophagy receptor (SAR) responsive to multiple cellular stresses 3. Therapeutically, NUFIP1-engineered exosomes from mesenchymal stem cells demonstrate potential in mitigating propofol-induced neurological injury in neonatal models 4. NUFIP1 emerges as a critical hub integrating ribosome metabolism, DNA damage surveillance, and immune homeostasis, with broad implications for sepsis, cancer, neurodegeneration, and gastrointestinal disease 5.