RB1CC1, also known as FIP200, is an essential macroautophagy/autophagy protein. It plays a significant role in a variety of biological and disease processes through its canonical autophagy-dependent and-independent functions. RB1CC1 is a subunit of the ULK1 complex in more complex eukaryotes and is proposed to be a functional homolog of the yeast Atg17 and Atg11 scaffolding proteins [2,3].

In tumour cells, lipid ROS upregulates RB1CC1, and the nuclear translocation of phosphorylated RB1CC1 at Ser537 is essential for sensitising ferroptosis. Nuclear RB1CC1 recruits ELP3 to enhance H4K12Ac histone modifications within enhancers related to ferroptosis, stimulating the transcription of ferroptosis-associated genes like CHCHD3, which in turn elevates mitochondrial ROS early after ferroptosis induction. In mice, Rb1cc1 is essential for ferroptosis agonists to suppress liver tumourigenesis [1]. Also, in Parkinson disease-related research, two different axes, CALCOCO2-RB1CC1 and OPTN-ATG9A, can initiate de novo biogenesis of autophagic membranes on ubiquitin-coated damaged mitochondria, highlighting RB1CC1's role in mitophagy [4].

In conclusion, RB1CC1 is crucial for autophagy-related functions and is involved in important cellular processes such as ferroptosis and mitophagy. Model-based research, especially the use of mouse models, has revealed its significance in tumour treatment and neurodegenerative disease-related processes, providing valuable insights into potential therapeutic targets for these diseases.