Abstract
BACKGROUND: Nuclear FMR1-interacting protein 1 (NUFIP1), originally identified as a binding partner of the fragile X mental retardation protein (FMRP), has increasingly been recognized as a pivotal factor in various pathological processes. Its recently elucidated role as a receptor in ribophagy positions it at the intersection of critical cellular pathways, suggesting broad functional significance in human disease pathogenesis. This review synthesizes emerging evidence underscoring the multifaceted involvement of NUFIP1 in key physiological and pathological mechanisms. It regulates fundamental processes such as tumor metabolism, immune responses during sepsis, and recovery from neural injury. Notably, recent findings indicate that impaired NUFIP1 function, particularly within the DNA damage response (DDR) pathway, can be exacerbated by external factors like low-protein diets, leading to exacerbated intestinal inflammation and the promotion of necroptosis. This compilation critically evaluates the mechanistic contributions of NUFIP1 across these diverse disease contexts and assesses its potential as a therapeutic target or biomarker. SHORT CONCLUSION: In conclusion, NUFIP1 emerges as a critical molecular player with widespread implications for human health. A comprehensive understanding of its functions provides valuable insights for developing novel therapeutic strategies. This review consolidates the current knowledge on NUFIP1, highlights its clinical relevance, and identifies promising avenues for future research to fully delineate its therapeutic potential.