NUFIP2, also known as nuclear FMR1 interacting protein 2, is involved in multiple biological processes. It is a core stress granule (SG) protein and participates in regulating protein translation and the integrated stress response. NUFIP2 also contributes to MTOR inactivation via the Ragulator-RRAGA-RRAGB complex during lysosomal damage [1,2]. Additionally, it binds to Roquin to promote recognition and regulation of ICOS mRNA, and is part of the FMRP interactome, suggesting its role in RNA-related functions [3,4].

In lysosomal damage models, mammalian ATG8s interact directly with NUFIP2, and Atg8ylation is needed for its recruitment to damaged lysosomes. NUFIP2 then contributes to mTOR inactivation, showing its role in coordinating SG and mTOR responses to lysosomal stress [1,2]. In Spinocerebellar Ataxia type 2 (SCA2) mouse models, ATXN2-polyQ expansion triggers NUFIP2 accumulation, indicating its potential involvement in this disease-related process [5].

In conclusion, NUFIP2 is crucial for processes like stress granule formation, MTOR regulation during lysosomal damage, and mRNA regulation. Studies using mouse models such as those related to lysosomal damage and SCA2 have revealed its role in these specific biological and disease-related contexts, contributing to our understanding of relevant molecular mechanisms.